Harel Yoon syndrome (ATAD3A mutation)

Inspired by a patient

Harel T, Yoon WH, Garone C, Gu S, Coban-Akdemir Z, Eldomery MK, Posey JE, Jhangiani SN, Rosenfeld JA, Cho MT, Fox S, Withers M, Brooks SM, Chiang T, Duraine L, Erdin S, Yuan B, Shao Y, Moussallem E, Lamperti C, Donati MA, Smith JD, McLaughlin HM, Eng CM, Walkiewicz M, Xia F, Pippucci T, Magini P, Seri M, Zeviani M, Hirano M, Hunter JV, Srour M, Zanigni S, Lewis RA, Muzny DM, Lotze TE, Boerwinkle E; Baylor-Hopkins Center for Mendelian Genomics; University of Washington Center for Mendelian Genomics; Gibbs RA, Hickey SE, Graham BH, Yang Y, Buhas D, Martin DM, Potocki L, Graziano C, Bellen HJ, Lupski JR. Recurrent De Novo and Biallelic Variation of ATAD3A, Encoding a Mitochondrial Membrane Protein, Results in Distinct Neurological Syndromes. Am J Hum Genet. 2016 Oct 6;99(4):831-845. doi: 10.1016/j.ajhg.2016.08.007. Epub 2016 Sep 15. PMID: 27640307; PMCID: PMC5065660.

Abstract

ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane protein implicated in mitochondrial dynamics, nucleoid organization, protein translation, cell growth, and cholesterol metabolism. We identified a recurrent de novo ATAD3A c.1582C>T (p.Arg528Trp) variant by whole-exome sequencing (WES) in five unrelated individuals with a core phenotype of global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. We also describe two families with biallelic variants in ATAD3A, including a homozygous variant in two siblings, and biallelic ATAD3A deletions mediated by nonallelic homologous recombination (NAHR) between ATAD3A and gene family members ATAD3B and ATAD3C. Tissue-specific overexpression of borR534W, the Drosophila mutation homologous to the human c.1582C>T (p.Arg528Trp) variant, resulted in a dramatic decrease in mitochondrial content, aberrant mitochondrial morphology, and increased autophagy. Homozygous null bor larvae showed a significant decrease of mitochondria, while overexpression of borWT resulted in larger, elongated mitochondria. Finally, fibroblasts of an affected individual exhibited increased mitophagy. We conclude that the p.Arg528Trp variant functions through a dominant-negative mechanism that results in small mitochondria that trigger mitophagy, resulting in a reduction in mitochondrial content. ATAD3A variation represents an additional link between mitochondrial dynamics and recognizable neurological syndromes, as seen with MFN2, OPA1, DNM1L, and STAT2 mutations.

Yap ZY, Park YH, Wortmann SB, Gunning AC, Ezer S, Lee S, Duraine L, Wilichowski E, Wilson K, Mayr JA, Wagner M, Li H, Kini U, Black ED, Monaghan KG, Lupski JR, Ellard S, Westphal DS, Harel T, Yoon WH. Functional interpretation of ATAD3A variants in neuro-mitochondrial phenotypes. Genome Med. 2021 Apr 12;13(1):55. doi: 10.1186/s13073-021-00873-3. PMID: 33845882; PMCID: PMC8042885.

Abstract

Background: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

Methods: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. A Drosophila Atad3a Gal4 knockin-null allele was generated using CRISPR-Cas9 genome editing technology to aid the interpretation of variants.

Results: We report 13 individuals from 8 unrelated families with biallelic ATAD3A variants. The variants included four missense variants inherited in trans to loss-of-function alleles (p.(Leu77Val), p.(Phe50Leu), p.(Arg170Trp), p.(Gly236Val)), a homozygous missense variant p.(Arg327Pro), and a heterozygous non-frameshift indel p.(Lys568del). Affected individuals exhibited findings previously associated with ATAD3A pathogenic variation, including developmental delay, hypotonia, congenital cataracts, hypertrophic cardiomyopathy, and cerebellar atrophy. Drosophila studies indicated that Phe50Leu, Gly236Val, Arg327Pro, and Lys568del are severe loss-of-function alleles leading to early developmental lethality. Further, we showed that Phe50Leu, Gly236Val, and Arg327Pro cause neurogenesis defects. On the contrary, Leu77Val and Arg170Trp are partial loss-of-function alleles that cause progressive locomotion defects and whose expression leads to an increase in autophagy and mitophagy in adult muscles.

Conclusion: Our findings expand the allelic spectrum of ATAD3A variants and exemplify the use of a functional assay in Drosophila to aid variant interpretation.

Tawfik CA, Zaitoun R, Farag AA. Harel Yoon syndrome: a novel mutation in ATAD3A gene and expansion of the clinical spectrum. Ophthalmic Genet. 2023 Jun;44(3):226-233. doi: 10.1080/13816810.2023.2183223. Epub 2023 Mar 1. PMID: 36856321.

Abstract

Background: Harel-Yoon syndrome (HAYOS) is a recently described neurodevelopmental disorder characterized by psychomotor delay, truncal hypotonia, appendicular spasticity, and peripheral neuropathy. It is caused by mutations in ATAD3A gene located on chromosome 1p.36.33 whose functions include mitochondrial DNA stabilization, the regulation of mitochondrial fission/fusion, and cholesterol homeostasis.

Materials and methods: An 11-year-old male patient of consanguineous Egyptian parents, who present with neuroregression and ptosis along with progressive impaired vision, undergoes complete ophthalmological and neurological examination. Additionally, color fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) of both the macula and optic nerve head, full field electroretinogram (ERG), and visual field perimetry were obtained. Whole-exome sequencing and mitochondrial genome sequencing were done in a commercial laboratory from a peripheral blood sample.

Results: A novel mutation in ATAD3A gene c.624_644del was identified by whole-exome sequencing consistent with a diagnosis of Harel-Yoon Syndrome (HAYOS). The 11-year-old boy had characteristic features of neurodevelopmental delay, hypotonia, and peripheral neuropathy. However, we documented some novel features as fatiguable ptosis, facial weakness, progressive bulbar palsy, obsessive-compulsive disorder (OCD) in addition to cone system dysfunction.

Conclusion: Our study reports a novel mutation in ATAD3A gene and expands the clinical spectrum of Harel-Yoon Syndrome. Future research aiming at better understanding of gene function will lead to better genotype-phenotype correlation and could pave the way to more treatment options.

Skopkova M, Stufkova H, Rambani V, Stranecky V, Brennerova K, Kolnikova M, Pietrzykova M, Karhanek M, Noskova L, Tesarova M, Hansikova H, Gasperikova D. ATAD3A-related pontocerebellar hypoplasia: new patients and insights into phenotypic variability. Orphanet J Rare Dis. 2023 Apr 24;18(1):92. doi: 10.1186/s13023-023-02689-3. PMID: 37095554; PMCID: PMC10127305.

Abstract

Background: Pathogenic variants in the ATAD3A gene lead to a heterogenous clinical picture and severity ranging from recessive neonatal-lethal pontocerebellar hypoplasia through milder dominant Harel-Yoon syndrome up to, again, neonatal-lethal but dominant cardiomyopathy. The genetic diagnostics of ATAD3A-related disorders is also challenging due to three paralogous genes in the ATAD3 locus, making it a difficult target for both sequencing and CNV analyses.

Results: Here we report four individuals from two families with compound heterozygous p.Leu77Val and exon 3-4 deletion in the ATAD3A gene. One of these patients was characterized as having combined OXPHOS deficiency based on decreased complex IV activities, decreased complex IV, I, and V holoenzyme content, as well as decreased levels of COX2 and ATP5A subunits and decreased rate of mitochondrial proteosynthesis. All four reported patients shared a strikingly similar clinical picture to a previously reported patient with the p.Leu77Val variant in combination with a null allele. They presented with a less severe course of the disease and a longer lifespan than in the case of biallelic loss-of-function variants. This consistency of the phenotype in otherwise clinically heterogenous disorder led us to the hypothesis that the severity of the phenotype could depend on the severity of variant impact. To follow this rationale, we reviewed the published cases and sorted the recessive variants according to their impact predicted by their type and the severity of the disease in the patients.

Conclusion: The clinical picture and severity of ATAD3A-related disorders are homogenous in patients sharing the same combinations of variants. This knowledge enables deduction of variant impact severity based on known cases and allows more accurate prognosis estimation, as well as a better understanding of the ATAD3A function.

Child abuse controversy, continued

UF Health Jacksonville pediatrician, Dr. Barbara Knox, is facing staff accusations of bullying coworkers, violating patient privacy and making racist remarks.

In June 2022, UF Health Jacksonville hired Knox to serve as a physician at the First Coast Child Protection Team, which treats children suspected of facing abuse.

Knox’s hiring at UF raised eyebrows given her controversy-marred professional history. In both Wisconsin and Alaska, the doctor faced complaints about workplace misconduct and misdiagnoses while serving in similar roles related to child abuse. Ultimately, she left both states amid investigations and lawsuits into her conduct.

Three staff members and one former staff member at First Coast Child Protection Team, who spoke anonymously for fear of retribution, shared accounts of Knox’s behavior.

New complaints

One employee, a longtime child welfare worker, said issues with Knox began around January 2024 when the doctor became chief of UF Health Jacksonville’s division of child protection and forensic pediatrics.

“She was targeting a lot of people… that had discussed her previous positions in Wisconsin and Alaska,” the welfare worker said. “She very quickly became highly interested in running them off.”

Knox asked employees to report on colleagues who the doctor viewed as a threat, instructing them to find any information that could potentially justify termination, according to the source.

This behavior became especially threatening when Dr. Mark Hudak, UF department of pediatrics chair, visited the CPT office to inform employees that he “personally vetted Dr. Knox” and that “anybody who’s speaking about her is subject to termination,” the welfare worker said.

One CPT employee recounted several instances in which Knox used her authority in the office for personal ends, including having employees drive her children places, insisting child abuse cases had to be scheduled around a 5K race and offering employees promotions in exchange for information about employees who opposed Knox.

“You don’t bring anything up to Dr. Knox; you’re afraid to get fired,” the CPT employee said. “You don’t say anything to her unless you want to look for another job.”

A second CPT employee said she had experienced similar interactions with Knox.

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“Only a few weeks after being employed there, I was summoned to her office privately, multiple times, with her requesting me to talk negatively and talk poorly about my supervisor so she had a reason to get them out of the office so she could kind of curate her own management,” she said. “She would practically back me into a corner.”

Those supervisors have since resigned due to the intimidation and pressure Knox placed upon them, she added.

Knox has also commented on employees’ skin color. The second CPT employee, who is mixed race, said Knox once asked her, “Why are you getting so dark?”

According to the first CPT employee, Knox complained that the receptionist for CPT’s Tallahassee office, a Black woman, looked “ghetto” due to having long, decorated fingernails.

In her account, Knox also wanted a case built against the Tallahassee receptionist and described her as “lazy” and someone who “looks like one of our clientele.”

The second CPT employee also said Knox had instructed her not to call her for any cases coming in past 10 p.m. A doctor is required to complete a patient examination before further medical actions can take place. The CPT employee received a call shortly after the 10 p.m. curfew was instigated about a child who was thrown head-first into a wall.

“Dr. Knox forbid me from calling her, so she’s now putting patients’ safety in jeopardy, because that kid should have gone to the hospital,” the CPT employee said.

The second CPT employee also said Knox’s conduct during sexual assault exams was inappropriate.

A mother brought her child in for an exam but said, due to her own experience of sexual assault, she could not watch. Instead, she would look away while remaining in the room for emotional support. The CPT employee relayed the request to Knox, who ignored it.

“Dr. Knox spread the child’s legs open in front of the mother… unclothed and put the child in the mother’s lap and started doing the swab,” the employee said. “The mom was just sitting there with tears down her face.”

Knox would treat families of color differently than white families, according to all three employees.

“We have African American, Hispanic, Muslim families that come in, and… she will go ahead and verify a report against them [over the smallest of issues], say it’s child abuse, and put the family in terrible, terrible situations,” one employee said.

When the child of a white doctor arrived to the clinic with gonorrhea — which is highly indicative of sexual abuse — Knox decided not to verify the case and claimed the child contracted gonorrhea from unwashed hands, the employee said.

Over 20 former CPT employees claimed to have quit over Knox’s conduct, according to both current and former employees.

One former employee who resigned described Knox’s behavior as “constant berating.”

“She would scream and yell and tell me what a terrible person I was,” the former employee, who worked under Knox in Florida, said.

Ultimately, the employee said the abuse broke her down to the point she had to resign.

UF public records revealed employees have also filed complaints to the Florida Office of Inspector General.

An anonymous complainant stated “[Knox] steps outside the guidelines of child welfare protocols, making inappropriate and unprofessional comments to colleagues and other agencies,” and she had stolen others’ work to create “presentations or published work about cases she was not directly associated with.”

On March 7, another complainant reported to UF’s Human Resources Department that Knox jumped to conclusions about a child’s injuries, labeling them as indications of abuse without examining the child’s full medical history.

“She took a small set of data and decided on a story of abuse without bothering to zoom out and investigate all possible reasons,” the report said.

According to the complainant, the child had a medical condition which provided a non-abuse cause of the child’s injuries.

“[Knox’s] bias on abuse leads her to find it where it doesn’t truly exist,” the complainant wrote.

A troubled history

The complaints workers at CPT have brought against Knox closely reflect those raised by her past employees in Wisconsin and Alaska.

In 2019, Knox left her position leading the University of Wisconsin’s Child Protection Program after the university placed her on paid leave while investigating complaints that she had bullied colleagues. In the letter UW sent to Knox notifying her of her paid leave status, the university explained that part of its decision was due to concerns about “unprofessional acts that may constitute retaliation against and/or intimidation of internal and external colleagues.”

One of Knox’s UW colleagues, Dr. Michael Stier, said he felt Knox had pressured him to make inaccurate abuse diagnoses, according to an article by the Wisconsin Watch. Wisconsin families filed lawsuits against Knox after her medical opinions caused them to lose custody of their children and, in some cases, even serve time in jail.

In Alaska, Knox led Alaska CARES, a child abuse clinic servicing the state. Investigations into Knox’s conduct there found that the clinic's entire medical staff had either quit or been fired in the two years Knox had worked there and staffers had complained once again of inaccurate medical diagnoses.

What’s next?

Neither Knox nor Hudak responded to requests for comment via email and phone call, though UF Health Jacksonville media relations manager Dan Leveton confirmed they received both. Leveton instructed that all communications related to Knox should come through the university via UF spokesperson Steve Orlando.

In an email statement, Orlando said Knox was hired due to her expertise and “positive contributions on behalf of children.”

“Dr. Knox is a key part of the faculty, and since her arrival her background and understanding in the field have enhanced our program and have made the community a safer place for children and their families,” Orlando wrote. As for allegations of Knox’s misconduct, he added, “the university does not comment on personnel matters.”

Several current and former employees confirmed that UF has launched an internal investigation, though with seemingly little results.

According to a former employee, one of UF’s investigators privately suggested that “it’s time to go public.”

University involvement has not inspired confidence among CPT employees concerned with Knox’s behavior.

“We do feel like the university has been negligent and nobody will step up to the plate [to address Knox’s behavior],” a welfare worker said. “She’s gotta go.”

Avery Parker

https://www.alligator.org/article/2025/01/uf-health-physician-accused-of-misconduct

Child abuse controversy

A controversial doctor. A disputed abuse diagnosis. Two convicted Wisconsin men say they are innocent

Wisconsin Watch

May 2, 2022

This story was produced by Wisconsin Watch, a nonprofit, nonpartisan investigative reporting organization that focuses on government integrity and quality of life issues in Wisconsin.

Dakota Black and Joshua Gehde are in prison for homicide after former UW Dr. Barbara Knox accused them of inflicting abusive head trauma.

By Brenda Wintrode, Wisconsin Watch

Nearly nine years after her son, Brayden, died, Shannon Turnbill still replays the image of the 5-year-old lying on the bed, unresponsive.

“It’s a picture I’ll never get out of my head,” she said of the encounter in October 2013. “His eyes were rolled back. It almost looked like he was having a seizure but not moving.”

After a University of Wisconsin doctor trained in identifying child abuse said Brayden had suffered from abusive head trauma, law enforcement blamed the only adult home with Brayden: Turnbill’s boyfriend, Dakota Black of Sun Prairie, Wisconsin.

In April 2016, Josh Gehde found his girlfriend’s 2-year-old daughter lying lifeless on the floor of their Madison, Wisconsin, apartment. Just minutes before, Gehde had given the toddler crackers and went to the bathroom to shave. When he came out, he saw chewed-up crackers on the rug near her face. He turned over her already cold body, struck her back to dislodge food and called 9-1-1.

The 9-1-1 operator coached him through CPR as he waited for paramedics. The girl died two days later after being removed from life support. Dr. Barbara Knox, the same UW child abuse pediatrician from Black’s case — who has been suspended and investigated by two hospitals in two states — said abusive head trauma caused the brain injuries that killed the girl.

Courts, legal experts and medical specialists are increasingly scrutinizing the abusive head trauma diagnosis, an umbrella term that includes the controversial diagnosis of shaken baby syndrome, for lacking a scientific basis and criteria for diagnosis. Earlier this year, a New Jersey judge labeled abusive head trauma “junk science” and refused to allow testimony about the diagnosis in his courtroom.

In both cases, Knox said the injuries happened within minutes of the child’s collapse, blaming the last person with the child. Records show that police and prosecutors, confident in Knox’s credentials, looked no further.

During each trial, attorneys and experts battled for the jury’s trust.

In the Gehde case, prosecutors showed jurors photos of a small, lifeless body still on life support, and in Black’s case, painted him as someone Brayden feared. Knox testified to a “reasonable degree of medical certainty” that each child died from abuse. Defense experts, who specialized in pediatric neurology and forensic neuropathology, blamed other possible conditions, saying they saw no signs of abuse.

“It would be most unusual to have a fatal head injury without an obvious large bruise on the scalp and a skull fracture,” Black’s expert, neuropathologist Dr. Jan Leestma, said in a report. “This child doesn’t have any of these things.”

But in the end, the juries in both cases believed Knox.

Black and Gehde are serving lengthy sentences in Wisconsin prisons, convicted of murdering the children in their care. They pleaded not guilty and refused prosecutors’ plea deals, despite facing decades behind bars. Both have lost their appeals.

The men insist they are innocent. Some family members of the children who died, including Turnbill, say they do not believe these men killed the children.

And Wisconsin Watch has identified at least eight cases in which Knox determined a child had suffered head trauma from abuse that investigators and medical specialists said were caused by benign medical conditions, injuries from severe birth trauma, accidental falls, a bleeding disorder and a possible stroke.

Knox did not respond to attempts to reach her for comment.

A national debate

These controversies are not unique to Wisconsin. In late April, a Texas appeals court halted the execution of Melissa Lucio, convicted of killing her 2-year-old daughter — a death the state’s medical examiner said was caused by “blunt force trauma” to the head in 2007.

Lucio and other family members had told police the girl fell down the stairs and was not abused — but then Lucio confessed to killing her after five hours of interrogation. The high court, citing several factors including Lucio’s possible innocence, sent the case back to a lower court for review.

Nationally, since 1992, 26 people have been exonerated following convictions on charges stemming from diagnoses of abusive head trauma or shaken baby syndrome, according to The National Registry of Exonerations.

The human instinct to protect children can snowball momentum around a child abuse allegation, making it “all too easy to sweep innocent people up in the process,” said Keith Findley, co-founder of the Wisconsin Innocence Project, who has written extensively about the problems of this type of diagnosis.

Knox’s fraught tenure

During her 13-year tenure in Wisconsin, Knox acted as a crucial liaison between the UW’s Child Protection Program and law enforcement, providing medical diagnoses, consultations or expert testimony in over 200 criminal cases, according to open records responses from 14 district attorneys in southern and central Wisconsin and an analysis of electronic court records by Court Data Technologies.

One of about 350 nationally certified child abuse pediatricians trained in recognizing child maltreatment and legal proceedings, Knox led the UW program until 2019, leaving after the hospital investigated whether she bullied her colleagues. Alaska CARES hired her that same year to lead the state’s forensic child abuse clinic. A joint investigation by Wisconsin Watch and the Anchorage Daily News found Knox generated similar allegations there.

During her brief tenure, the entire medical staff of Alaska CARES left or had their jobs reassigned. Knox submitted her resignation from Alaska CARES in January, scheduled to take effect on April 1. In March, online records show Knox was issued a medical license in Florida.

In all, the joint investigation also found 12 cases in which Knox’s diagnoses of abuse were rejected by juries, court officials, child welfare workers, investigators and other doctors.

Knox tied to 124 Dane County cases

But hundreds more cases funneled into the criminal justice system.

Dodge County District Attorney Kurt Klomberg said he stopped using Knox as an expert in 2017 after she failed to provide a timely report in an abusive head trauma case. He said he decided not to “support any child abuse or neglect cases for prosecution based on the work of Dr. Knox unless she had completed an opinion report prior to the decision to charge.”

Klomberg said he also advised law enforcement and human services to seek experts from other hospitals. After he made that decision, Klomberg got one referral for child neglect that Knox alleged. He declined to pursue it for lack of evidence.

“I seek to engage medical experts who I can rely upon,” Klomberg added. “I determined that I would not likely support a case involving Dr. Knox’s independent opinion several years ago.”

Juneau County District Attorney Kenneth Hamm said his office still has pending cases that originated on Knox’s medical opinions. After Knox left Wisconsin, he requested second opinions from other doctors, which Hamm said were “generally in line with what Dr. Knox stated and did not change the outcomes.” He added that none involved abusive head trauma or shaken baby syndrome.

Hamm and Portage County District Attorney Louis Molepske Jr. both told Wisconsin Watch they would consider re-examining closed cases if new evidence or concerns about Knox’s diagnoses emerge.

Of the 208 cases found by Wisconsin Watch, the Dane County District Attorney’s Office brought 124, over 70% of them since Ismael Ozanne’s election in 2010.

In an interview, Ozanne expressed confidence in convictions made by his office involving Knox’s diagnoses and said reviewing the cases because of questions about Knox’s job performance was an “oversimplification.”

“We were not just speaking with Dr. Knox alone,” Ozanne told Wisconsin Watch. “We were having to reach out to other experts . . . And, to my knowledge, none of those diagnoses were ever called into question. The hospital has never called us and said any of these diagnoses you should be worried about to my knowledge; and law enforcement has not reached out to us to say there’s other evidence that we have that basically shows that what was referred to you is false.”

Ozanne said he had not reached out to the UW to discuss possible misdiagnosis, adding, “I would assume if there were questions, they would reach out to us.”

Findley said the fact other doctors agreed with Knox “does not resolve the matter” because of the “repeated allegations and findings that Dr. Knox bullied colleagues” and that “plenty of other doctors and experts have raised concerns about some of her determinations.”

Findley described Knox as “an unusually aggressive and prolific advocate for concluding a child was the victim of abuse on vague, non-specific medical findings, which the research shows can have multiple etiologies, not just abuse.”

The hospital and law enforcement not alerting Ozanne to possible mistakes is “hardly surprising,” given the potential legal liability, Findley said. He added that Knox’s work history “ought at the very least prompt serious concerns about what wreckage she might have left in her wake in this jurisdiction,” he said.

Four witnesses noticed something off

The day Brayden Turnbill collapsed, his mother remembers her son waking up “happy.” She helped Brayden dress in one of his favorite superhero T-shirts and tied his shoes. The little boy who loved the Teenage Mutant Ninja Turtles and the Green Bay Packers had yet to master shoelaces.

Four people who saw Brayden after school that day told Sun Prairie police they noticed something off with the normally cheerful, fun-loving kindergartner. Two, who were children, described Brayden as looking “sad,” and as if he had been “crying without tears.”

Black said he repeatedly asked Brayden if he was OK after he came home from school with “bloodshot” eyes and acting “whiny.” Patricia Garwo, Turnbill’s cousin who picked Brayden and her children up from the bus that day, also asked him several times if he was alright, according to police reports.

The boy’s 5-year-old cousin told police that she twice saw Brayden fall on the playground. The following year an investigator for the defense reported more detail: “She said Brayden fell once off the gray monkey bars and landed on his knees, and fell once off the red monkey bars and landed on his feet . . . She said she saw with her own eyes that Brayden hurt his back, and almost his arm, on the big gray pole.” The girl said Brayden told the teacher supervising recess and went to the school nurse.

But the jurors who convicted Black never heard the girl’s testimony. Dane County Circuit Judge Stephen Ehlke barred details of the reported fall, ruling it irrelevant since she did not see Brayden hit his head.

Once he got home from school, Brayden visited a neighbor’s house briefly, played for about 15 minutes with his infant brother before telling Black he was tired and going downstairs for a nap.

Black told police he stayed upstairs with couple’s baby. The next time he saw Brayden was after Turnbill found him unresponsive in his bed.

Devastating news

As the mother of eight children, Turnbill saw some of Brayden’s older siblings experience fever-induced seizures when they were young. But when Brayden didn’t recover as her other children had, Turnbill yelled for Black to call 9-1-1. When she got on the phone, the operator walked her through CPR. And when she lifted his shirt she and Black saw a diagonal mark across his chest. Black said it looked like “he got hit with a stick.”

Doctors at St. Mary’s Hospital in Madison rushed Brayden by helicopter to the UW where doctors performed emergency brain surgery in an unsuccessful attempt to save his life. Turnbill followed with a friend to the UW.

Once there, Turnbill recalled how Knox delivered the devastating news: “We did what we could, but Brayden’s gone.” Turnbill remembered sliding off the chair to her knees and wailing.

Abuse was the only possible explanation for her son’s death. “ ‘Whoever was the last person with him is the one who did this.’ That’s exactly what she said,” Turnbill recalled.

Turnbill will never forget what Knox said next. Still standing over the grieving mother, the doctor said Brayden had bleeding on his brain “so severe that, that his, his brain pretty much fell into two pieces.”

Turnbill stammered as she recounted the episode almost nine years later, asking:

“How the hell are you going to come in and tell a mother that about her son?”

Police: ‘She has credentials’

After questioning Black at home for hours, police arrested him on an outstanding probation violation for a drug charge and took him to the Sun Prairie Police Department.

Detective Frank Smith ran the interrogation. He told Black he believed everything Knox told police — the boy’s collapse from a massive brain injury happened within minutes of being abused, according to a transcript.

“She’s an expert in her field,” Smith told Black. “She’s an expert witness for the state of Wisconsin. Okay? She has credentials.”

Then the officer added: “Something happened in the house. You did something to him.”

After Black denied harming Brayden — “I love that kid like he’s my own son” — the officer would have none of it.

“If I had any doubt or reserve of what she (Knox) told me, I wouldn’t be accusing you of doing this,” Smith said. “But I am because I believe her. I have that much faith in her science and her training.”

Black told Wisconsin Watch in a phone interview from Green Bay Correctional Institution that the interrogation was “intimidating” but “I wasn’t really scared, because . . . I didn’t have anything to hide.”

In court, Knox and pediatric radiologist Dr. Wilbur Smith testified for the state that the bruise across the boy’s chest looked to them like a “loop-mark injury” from someone striking him with a cord, like an extension cord or cell-phone charging cord. A police search of the home failed to find a cord fitting Knox’s description.

Ehlke’s ruling barring the testimony about falls on the playground kept defense experts from discussing how short falls can sometimes cause serious brain injuries in children, and in rare cases, death. In 12 of the 18 cases cited in that study, the children experienced a “lucid interval” of as long as two days before collapsing.

Knox acknowledged the possibility of lucidity between injury and collapse and referenced the 2009 death of actress Natasha Richardson, whose health declined hours after hitting her head in a skiing accident and died two days later.

Asked whether that could have happened in Brayden Turnbill’s case, Knox responded: “Absolutely not” — because their brain bleeds occurred within different, yet proximal, layers of the brain. However, a 2018 Medscape article reported that more than half of the patients who had the same type of bleeding as Brayden “had lucid intervals and were able to make conversation between the time of their injury and subsequent deterioration.”

Black was convicted after a nine-day trial in Dane County Circuit Court. Turnbill refused to testify for the prosecution. “I still believe that something happened to him at school,” she said.

Black, now 32, won’t get out of prison until 2045. Then, he faces 21 more years of community supervision, finishing his sentence at age 76.

‘It was the scariest thing ever’

Joshua Gehde said he never minded watching his girlfriend’s daughter, who he described as “very bubbly, happy, always smiling.”

The three had lived together for six months in an apartment near Madison’s Reindahl Park. They loved to visit the city’s botanical garden and just get outside together, he said.

“It felt like we were becoming a family, like everything was coming into place,” Gehde said during a phone interview from Stanley Correctional Institution.

On the morning the 2-year-old collapsed, his girlfriend went to work, and Gehde took the toddler to the park. He snapped a photo of the girl with a pacifier in her mouth, wisps of blond hair surrounding her face beneath the hood of her pink coat, and sent it to her mother.

After about an hour at the park, they went back home for lunch. He broke up some Ritz crackers on the highchair tray and put it on the floor where she could reach. He heard her cough a few times while he was in the bathroom but “didn’t think anything of it,” he told police. He thought she was fine. Minutes later, she wasn’t.

A paramedic who arrived at the scene said the girl’s lips were blue, and a firefighter reported using forceps to remove regurgitated food from her airway. A police officer who arrived on the scene originally concluded the event was a “tragic accident,” according to court documents.

Two days later, the girl died at the UW. Doctors reported the girl had brain and eye bleeding and brain swelling. Knox documented multiple bruises, including on the back of the girl’s head, and a large red mark on the girl’s left buttock she described as a “handprint.” Citing the brain and eye findings as a “constellation” of injuries, and marks she labeled as bruises, Knox declared the girl suffered “definite abusive head trauma.”

The day after the toddler died, Gehde, shackled at the wrists and ankles and wearing blue prison scrubs, shuffled into a Dane County Sheriff’s Office interrogation room. The then-25-year-old and two Madison police detectives sat on upholstered furniture, a coffee table between them, while he recounted the events leading up to the girl’s collapse.

At the request of detectives, he reenacted how he gave her back blows to dislodge the food from her throat on a toddler-sized mannequin.

“It was the scariest thing ever . . . she was lifeless,” he told the Madison detectives, as he sat back on the couch and reached for tissues to dry his eyes.

But detectives rejected his story based on what Knox told them. “We know for sure the doctors are going to say she didn’t choke on anything,” Detective Maya Krajcinovic said.

Since Gehde was the last one with her, he was the only one who could tell them what happened, they said.

“I’m not going to admit to something I didn’t do,” Gehde said, dissolving into tears. “I f***ing loved that girl.”

Later in the interview, Krajcinovic picked up the mannequin to demonstrate what she thought could cause the girl’s injuries. “If somebody grabs a kid and gets upset,” she said, shaking the dummy, its head flailing back and forth, then strikes its head on a couch, “ … that’s what causes bruises.”

Gehde looked at her confused and asked, “Who does that though?”

Defense offers other causes

Three medical specialists hired by the defense testified the girl died after blood clots in her brain caused a seizure, starving her brain and heart of oxygen. A neuroradiologist said small seizures can mimic a choking incident. And the girl’s autopsy report revealed she had bitten her tongue, a common occurrence in children having seizures.

Pediatric neurologist Dr. Joseph Scheller, said he could not determine if the clots were hours or days old. Regarding her bruises, he wrote 2-year-olds “can easily become bruised while engaging in play activities.”

In her medical report, Knox acknowledged the girl’s brain scan showed blood clots and bleeding throughout her brain, but, coupled with the child’s multiple bruises, concluded the girl’s brain injury was due to abusive head trauma.

During a cross-examination at trial, Gehde’s attorney asked Knox if she’s ever made a mistake.

“I am not aware that I have ever had a mistaken diagnosis,” she answered.

Gehde and other members of his family independently told Wisconsin Watch that the day after his defense team’s experts testified, some of the girl’s family members, including the child’s mother, switched sides and sat near Gehde’s parents and his defense attorneys.

If he had pleaded guilty, Gehde said both families would have “never heard any of this, they would have never heard the evidence to let them know I didn’t do anything — for them to support my innocence.”

The girl’s mother did not respond to interview requests, and attempts to interview other family members were unsuccessful. Private messages shared with Wisconsin Watch between the Gehde family and some of the girl’s family members, as recently as 2020, revealed they believed Gehde is innocent.

However, the jury did not.

Gehde’s 20-year prison sentence ends in 2039, followed by 15 years of probation. He unsuccessfully appealed in 2019.

He wrote in an email from prison: “My whole life was stripped from me for something I didn’t do.”

Separated — but still close

Less than one year after Brayden died, a consultant hired by the Sun Prairie School District inventoried the district’s playground equipment. The study listed — in poor condition and as a high priority for replacement — three district play structures, one of which was the monkey bars from which the girl said she saw Brayden fall.

A spokeswoman for the school district refused to answer questions about Brayden’s reported fall from the Royal Oaks Elementary School playground structure and the timing of the consultant’s hiring.

Black and Turnbill remain close and are trying to raise their two sons together, although the prison has banned her from visiting him because he was convicted of killing her son.

Black talks to his sons several times a week on Turnbill’s phone. The boys, who are now 9 and 8, know their father is in prison because of something that happened to their brother, but she has spared them the details.

She tells them, “The police don’t always tell the truth . . . the lawyers, the judges; the news doesn’t always tell you the truth.”

After Brayden died, Shannon and the boys lived with Black’s mother for three years, but have since moved from one living situation to the next. She now works as a housekeeper in a Madison hotel and rents a room there for her and the boys while she tries to get subsidized housing.

She hopes in sharing her story she can uncover the truth of what happened to her son that day — and find some justice for Black.

“Someday, I hope they figure out what really happened, and let him go.”

The Fund for Investigative Journalism provided financial support for this story. The nonprofit Wisconsin Watch (www.WisconsinWatch.org) collaborates with WPR, PBS Wisconsin, other news media and the University of Wisconsin-Madison School of Journalism and Mass Communication. All works created, published, posted or disseminated by Wisconsin Watch do not necessarily reflect the views or opinions of UW-Madison or any of its affiliates.

https://wnanews.com/2022/05/02/a-controversial-doctor-a-disputed-abuse-diagnosis-two-convicted-wisconsin-men-say-they-are-innocent/

11 days without sleep

Lessons from sleeplessness: The 60th anniversary of Randy Gardner's world record

January 28, 2024 6:36 PM ET

Heard on All Things Considered

By Ashley Montgomery

In December 1963, a military family named the Gardners had just moved to San Diego, Calif.

The oldest son, 17-year-old Randy Gardner, was a self-proclaimed "science nerd." His family had moved every two years, and in every town they lived in, Gardner made sure to enter the science fair.

He was determined to make a splash in the 10th Annual Greater San Diego Science Fair.

When researching potential topics, Gardner heard about a radio deejay in Honolulu, Hawaii, who avoided sleep for 260 hours.

So Gardner and his two friends, Bruce McAllister and Joe Marciano, set out to beat this record.

When asked about his interest in breaking a sleep deprivation record, Gardner said, "I'm a very determined person, and when I get things under my craw, I can't let it go until there's some kind of a solution."

Of his scientific trio, Randy lost the coin toss: He would be the test subject who would deprive himself of sleep. His two friends would take turns monitoring his mental and physical reaction times as well as making sure Gardner didn't fall asleep.

The experiment began during their school's winter break on Dec. 28, 1963.

Three days into sleeplessness, Gardner said, he experienced nausea and had trouble remembering things.

Speaking to NPR in 2017, Gardner said:

"I was really nauseous. And this went on for just about the entire rest of the experiment. And it just kept going downhill. I mean, it was crazy where you couldn't remember things. It was almost like an early Alzheimer's thing brought on by lack of sleep."

But Gardner stayed awake.

The experiment gained the attention of local reporters, which, in Gardner's opinion, was good for the experiment "because that kept me awake," he said. "You know, you're dealing with these people and their cameras and their questions."

The news made its way to Stanford, Calif., where a young Stanford sleep researcher named William C. Dement was so intrigued that he drove to San Diego to meet Gardner.

Along with a U.S. Navy medic named Lt. Cmdr. John J. Ross, Dement helped monitor Gardner's health throughout the experiment. Dement also helped Gardner stay awake by playing basketball or games of pinball with Gardner.

When asked about his win percentage in pinball, Gardner said, "I did good. I think I beat him most of the time."

Gardner actually won all the time.

"Physically, I didn't have any problems," Gardner said. "But the mental part is what went downhill. The longer I stayed awake, the more irritable I got."

On Jan. 8, 1964, Gardner reached the last day of the experiment. He had been awake for 11 days straight — 264 hours — a new Guinness World Record.

Gardner said, "I had a very short fuse on day 11. I remember snapping at reporters. They were asking me these questions over and over and over. And I was just — I was a brat."

After talking with reporters, Gardner was sent to a nearby naval hospital. There, doctors observed his brain waves through an electroencephalogram machine he was hooked up to. Medically, Gardner was perfectly healthy.

So, at the naval hospital, Gardner slept for 14 hours. After he woke up, he said, he felt "groggy, but not any groggier than a normal person."

Although Gardner's record was broken within the same year, his experiment is one of the most well-documented cases of sleep deprivation. It supported later studies of "microsleeps." According to Guinness World Records, microsleeps are "momentary lapses into sleep that last for just a few seconds."

Decades later, the field of sleep research had grown exponentially, including the detrimental effects of sleep deprivation.

The last Guinness world record for sleep deprivation was awarded in 1986 to Robert McDonald, who deprived himself of sleep for almost 19 days. In 1996, the GWR stopped tracking sleep deprivation, citing the "harmful" effects of sleeplessness.

In making this decision, Craig Glenday, editor-in-chief of Guinness World Records, wrote:

"Sleep is just one of those key, absolute, fundamental parts of human nature — we need our sleep. And I think that's why this is a particularly fascinating record, because challenging the extremes of something that is so absolute is key to understanding who we are as a species."

When Gardner spoke to NPR in 2017, he mentioned that he developed insomnia as an adult. He said, "About 10 years ago, I stopped sleeping. I could not sleep. I would lay in bed for five, six hours, sleep maybe 15 minutes and wake up again. I was a – I was a basket case."

It's unclear what triggered his condition. But Randy Gardner says he sees it as some kind of "karmic payback" for his science experiment 60 years ago.

Head transplant 9

Startup claims they have created AI head transplant system, plans to perform first procedure within decade

By Elizabeth Karpen

Published May 22, 2024, 2:34 p.m. ET

Scientists put their heads together for an insane medical breakthrough.

Neuroscience and biomedical engineering startup BrainBridge announced that it has created an AI-mechanized system for performing head transplants.

The procedure would graft a head onto the body of a brain-dead donor, maintaining the memories, cognitive abilities and consciousness of the transplanted individual.

The researchers believe the innovative surgery would help patients with untreatable conditions like paralysis and certain cancers, as well as neurological diseases like Alzheimer’s and Parkinson’s.

Hashem Al-Ghaili, the scientist behind the project, said that the research has been evaluated by experts across multiple related fields.

“The goal of our technology is to push the boundaries of what is possible in medical science and provide innovative solutions for those battling life-threatening conditions,” Al-Ghaili told SWNS.

“Our technology promises to open doors to lifesaving treatments that were unimaginable just a few years ago,” he added.

BrainBridge plans to utilize surgical robots and artificial intelligence to reconstruct facial feature for full facial muscle use.

“The process employs advanced high-speed robotic systems to prevent brain cell degradation and ensure seamless compatibility, BrainBridge said in a statement.

“The entire procedure is guided by real-time molecular-level imaging and AI algorithms to facilitate precise reconnection of the spinal cord, nerves, and blood vessels.”

BrainBridge claims the first procedure will be conducted within eight years.

The company said it’s publicizing the procedure so far in advance to better attract top scientists to the project.

BrainBridge says that head transplants are only the beginning.

“In the short term, we expect the project to result in spinal cord reconstruction breakthrough and whole-body transplant but in the long term, the project will expand into areas that will transform healthcare as we know it.”

https://nypost.com/2024/05/22/us-news/scientists-announces-wild-plan-for-first-head-transplant/

Medical mayhem 17

A Texas-based doctor was sentenced Wednesday to 10 years in prison for healthcare fraud after he carried out what prosecutors said was a nearly two-decade scheme that involved falsely diagnosing thousands of patients with degenerative diseases and profiting handsomely off their treatments.

Jorge Zamora-Quezada, a rheumatologist licensed to practice medicine in Texas, Arizona and Massachusetts before being stripped of his licenses in each state, raked in hundreds of millions of dollars for the misdiagnoses and treatment he ordered during his roughly 20 years as a medical practitioner. The treatments included punishing rounds of chemotherapy, intravenous infusions, and a battery of other tests, monthly visits, and regular procedures associated with the treatment of rheumatoid arthritis, a chronic, autoimmune condition for which there is no cure.

The sentencing, and his earlier court appearances, played out at times like a study in contrasts. Prosecutors detailed his extravagant lifestyle, including a private jet, 13 properties across the U.S., including in Aspen and various towns in Mexico, and a Maserati – while the health of the patients he defrauded continued to worsen.  

Prosecutors accused him of taking advantage of vulnerable individuals in Texas, such as teenagers, elderly individuals, and disabled persons, in order to carry out the scheme. Some of them testified at Wednesday’s hearing about the ongoing side effects they suffered as a result of the doctor’s actions, including receiving chemotherapy or IV infusions they did not need. 

It’s "one of the most egregious" cases of its kind the Justice Department has brought in this space, Matthew Galeotti, head of the Justice Department Criminal Division, told Fox News Digital in a sit-down interview on Wednesday.

That’s because of "all of the various kinds of misconduct rolled into one," he said, "and because it was pervasive – the scheme lasted more than 18 years."

"By the time you're towards the end of the scheme, he knows the consequences some of these things have had on the victims, and he's going forward anyways," he said of the doctor.

The Justice Department's Criminal Division has been prosecuting this case for years. Unlike other departments, it is one of the few where career and political staff alike are largely in lockstep, with goals and cases that transcend partisan politics and seek instead to hold criminals like the Texas doctor accountable. 

Galeotti said he sees the case as emblematic of the Trump administration’s goals to vindicate victims and counter wasteful government spending.

"Even in cases where you don't see this level of misconduct, where you're not prescribing someone chemotherapy medicine that doesn't need it, which obviously sort of stands out on its own, we still have a problem because you were wasting government funds that should be going to actually benefiting patients," Galeotti said.

A separate Justice Department official told Fox News Digital Zamora-Quezada’s case was one of the "most significant" instances of patient harm that he had seen in at least a decade.

"There was testimony about truly debilitating side effects from the medications, things like strokes, necrosis of the jawbone, really the jawbone melting away, hair loss, liver damage," the official said. 

The doctor’s actions were seen as particularly egregious, in the Justice Department's telling, because they sought to prey on lower-income communities in Texas, targeting teenagers, elderly persons, and disabled individuals. The doctor also operated in areas with less access to medical care and with fewer native English speakers compared to other parts of the state.

"Of course, it's always the most twisted when you're benefiting from someone else's misfortune – misfortune you caused – and misfortune you used for your own personal enrichment," Galeotti said.

"They're the hallmarks of the worst kind of conduct that you see," Galeotti said.

Zamora-Quezada was convicted by a jury in 2020 of seven counts of healthcare fraud, one count of conspiracy to commit healthcare fraud, and one count of obstruction of justice. His attorneys argued that the fraud was not "pervasive" in the way the government made it out to be, according to public court filings.

Prosecutors said Zamora-Quezada purchased condominium properties in vacation towns, including in Aspen, San Diego, and Puerto Vallarta, Mexico. They said he commuted to his various doctors’ offices in Texas in a Maserati and a private jet, both emblazoned with his initials, "ZQ." His assets were forfeited after he was charged, prosecutors said.

Meanwhile, they said, while Zamora-Quezada was living a life of luxury, out of nearly 100,000 Medicare patients he treated, Zamora-Quezada diagnosed 72.9% of them with rheumatoid arthritis. Prosecutors compared that data to seven other Texas rheumatologists, who cumulatively diagnosed 13% of their patients with the same condition.

Prosecutors asked for $100 million in restitution, but the judge required him to pay $28 million.

Attorneys for Zamora-Quezada did not respond to Fox News Digital's request for comment.

Breanne Deppisch is a national politics reporter for Fox News Digital covering the Trump administration, with a focus on the Justice Department, FBI, and other national news. 

https://www.foxnews.com/politics/texas-doctor-sentenced-10-years-prison-one-most-significant-cases-patient-harm?dicbo=v2-26tF2JB

Smith-Lemli-Opitz syndrome

Kritzer A, Dutta R, Pramparo T, Terner-Rosenthal J, Vig P, Steiner RD. Smith-Lemli-Opitz Syndrome: Clinical, Biochemical, and Genetic Insights With Emerging Treatment Opportunities. Genet Med. 2025 Apr 29:101450. doi: 10.1016/j.gim.2025.101450. Epub ahead of print. PMID: 40314187.

Abstract

Smith-Lemli-Opitz syndrome (SLOS), also known as RSH syndrome, is an inborn error of cholesterol biosynthesis first described in 1964. Since then, significant advances have been made in understanding its pathophysiology, both during fetal development and postnatally. Cholesterol is a crucial lipid in the body, especially in the central nervous system, which accounts for nearly 25% of the body's total cholesterol. Cholesterol deficiency in SLOS can lead to congenital malformations and severe neurodevelopmental disabilities. The biochemical and genetic bases of SLOS have been elucidated. Reduced or absent 7-dehydrocholesterol reductase (DHCR7) enzymatic activity results not only in cholesterol deficiency but also in accumulation of 7-dehydrocholesterol, 8-dehydrocholesterol, and toxic oxysterol metabolites, which contribute to the pathophysiology of SLOS and correlate variably with the severity of its clinical symptoms. Despite decades of research, the clinical recognition of SLOS remains challenging due to the condition's multisystemic nature and noteworthy phenotypic variability. This review provides an up-to-date summary of major research advances in the study of SLOS with a focus on clinical manifestations and biochemical and genetic findings, which taken together facilitate recognition and diagnostic confirmation. Additionally, we recap past and current efforts in therapeutic development and offer guidance for disease management.

Korade Z, Anderson AC, Balog M, Tallman KA, Porter NA, Mirnics K. Hydroxyzine Effects on Post-Lanosterol Biosynthesis in Smith-Lemli-Opitz Syndrome (SLOS) Models. Biomolecules. 2025 Apr 10;15(4):562. doi: 10.3390/biom15040562. PMID: 40305315; PMCID: PMC12024545.

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is a developmental disability arising from bi-allelic pathogenic variants in the 7-dehydrocholestrol reductase (DHCR7) enzyme and the accumulation of 7-dehydrocholesterol (7-DHC). 7-DHC spontaneously oxidizes and gives rise to cytotoxic oxysterols. Our recent high-throughput screening on Dhcr7-deficient Neuro2a cells identified hydroxyzine (HYZ) as a medication that could counteract the high levels of 7-DHC. We assessed the effects of HYZ in Dhcr7-deficient Neuro2a cells, neuronal cultures and glial cultures from Dhcr7T93M/T93M transgenic mice, and human dermal fibroblasts from patients with SLOS. LC-MS/MS biochemical analyses revealed a strong modulatory effect of HYZ on post-lanosterol biosynthesis across all four SLOS models. However, the HYZ-induced biochemical changes were complex, dose-dependent, and variable across the four SLOS models. Dhcr7-deficient Neuro2a cells showed decreased 7-DHC, 8-dehydrocholesterol (8-DHC), and desmosterol (DES) levels (all p < 0.01), while neuronal and glial cultures from Dhcr7T93M/T93M transgenic mice reported 8 significantly altered analytes (all p < 0.001). Human dermal fibroblast from patients with SLOS reacted to HYZ exposure with significantly decreased 7-DHC, 7-dehydrodesmosterol (7-DHD), and dihydrolanosterol (DHL) levels (p < 0.001), coupled with elevation in zymosterol (ZYM), zymostenol (ZYME), and 8-DHC (p < 0.001). Further evaluations are required to determine if the potentially beneficial effects of decreased 7-DHC, 7-DHD and DHL levels in SLOS models and patient biomaterials are counteracted by the rise in other post-lanosterol intermediates.

Westbye AB, Dizdarevic LL, Dahl SR, Asprusten EA, Bliksrud YT, Sandblom AL, Diczfalusy U, Thorsby PM, Retterstøl K. A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndrome. J Lipid Res. 2025 Jan;66(1):100698. doi: 10.1016/j.jlr.2024.100698. Epub 2024 Nov 19. PMID: 39566847; PMCID: PMC11714705.

Abstract

Disease-specific sterols accumulate in the blood of patients with several rare lipid disorders. Biochemical measurement of these sterols is important for correct diagnosis and sometimes monitoring of treatment. Existing methods to measure sterols in blood, particularly plant sterols, are often laborious and time consuming. Partly as a result, clinical access to sterol measurements is limited in many parts of the world. A simple and rapid method to extract free sterols from human serum and quantitate their concentration using isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) without derivatization was developed. The method was designed to be compatible with routine workflows (e.g., 96-well format) in a clinical lab and extensively validated. Serum from at least 125 controls were analyzed and used to estimate the upper reference limits for sitosterol, campesterol, stigmasterol, desmosterol, 7-dehydrocholesterol (7DHC), lathosterol, and cholestanol. Serum from patients with the rare lipid disorders sitosterolemia (n = 7), Smith-Lemli-Opitz syndrome (SLOS; n = 1), and cerebrotendinous xanthomatosis (CTX; n = 1) were analyzed. All seven sitosterolemia patients had greatly elevated levels of free plant sterols (sitosterol, campesterol, and stigmasterol) compared to the controls. The SLOS serum contained massively increased concentrations of 7DHC. CTX serum contained greatly increased concentrations of cholestanol, as well as 7DHC and lathosterol. Spiking experiments indicated that the method is likely also useful for the diagnosis of desmosterolosis and lathosterolosis. The reported method is a relatively simple and fast LC-MS/MS method capable of quantitating diagnostically important sterols and differentiated patients with three rare lipid disorders from controls.

Delandistrogene moxeparvovec gene therapy in Duchenne muscular dystrophy

Oskoui M, Caller TA, Parsons JA, Servais L, Butterfield RJ, Bharadwaj J, Rose SC, Tolchin B, Puskala Hamel K, Silsbee HM, Dowling JJ. Delandistrogene Moxeparvovec Gene Therapy in Individuals With Duchenne Muscular Dystrophy: Evidence in Focus: Report of the AAN Guidelines Subcommittee. Neurology. 2025 Jun 10;104(11):e213604. doi: 10.1212/WNL.0000000000213604. Epub 2025 May 14. PMID: 40367405.

Abstract

This Evidence in Focus reviews the current evidence on the efficacy and adverse effects of delandistrogene moxeparvovec in patients with Duchenne muscular dystrophy (DMD) and presents clinical considerations regarding use. The author panel systematically reviewed available clinical trial data on delandistrogene moxeparvovec in patients with DMD. The risk of bias was evaluated using the American Academy of Neurology's 2017 therapeutic classification of evidence scheme. Safety information, regulatory decisions, and clinical context were also reviewed. Six clinical trials were identified, of which 4 had peer-reviewed data available. From the 4 studies with available data (2 Class I and 2 Class III), exposure data are available on 134 boys, of which 128 are ambulatory and aged ≥4 to <8 years. Both Class I studies failed to meet the primary functional motor outcome as assessed by change in the North Star Ambulatory Assessment score. Several secondary functional motor outcomes demonstrated improvement in the treatment group with small effect sizes, not meeting statistical significance from hierarchical analysis. Corticosteroid dose exposure was higher in the treatment group in the first 12 weeks after infusion, potentially contributing to measured differences between groups. Safety outcomes were similar across studies with multiple treatment-related adverse events, including peri-infusion effects, immune myositis and myocarditis, thrombocytopenia, and liver toxicity. One death has been reported in an individual who was treated with delandistrogene moxeparvovec outside of a trial. Despite not demonstrating efficacy in its primary outcome, delandistrogene moxeparvovec has been approved by the US Food and Drug Administration (FDA) for use in boys with DMD. This decision was supported by the relative safety of the product and secondary outcome measures data in the phase 3 clinical trial. As the drug may now be actively prescribed in the United States and other countries after FDA approval, providers should be aware of the limitations of the treatment and the need to monitor for immune-related side effects including myocarditis, liver injury, and thrombocytopenia, which may require expanded clinical infrastructure. Additional clinical trials and careful collection of real-world evidence from treated patients will be essential to establish short-term and long-term effectiveness and inform understanding of benefits and risks of delandistrogene moxeparvovec across the lifespan.

Why autism cases have risen so much since the ‘90s

Why autism cases have risen so much since the ‘90s — and 3 common myths to ignore

By Dr. Rebecca A. Shalev and Dr. Kritika Nayar

Autism, or autism spectrum disorder, has been a topic in the news a lot recently, yet the complex neurological condition remains widely misunderstood.

Autism is a difference in how someone’s brain works that shapes how they interact with the world. Clinically, it’s a disorder that affects brain development and causes social communication and behavioral differences. With such a wide range of traits, autism truly is a spectrum.

Gaining a deeper understanding of these nuances is key. We address some common myths and offer guidance on supporting children and families after a diagnosis.

What causes autism?

There is no single known cause of autism. Given its complexity and the wide range of symptoms, it’s likely that multiple factors contribute. This neurodevelopmental difference is something children are born with — it has nothing to do with parenting style, vaccines or foods.

Research suggests that genetic and environmental factors may contribute to the risk of developing autism. When we say autism is genetic, we mean that variations in certain genes can influence how a baby’s brain develops.

These variations may occur spontaneously or be inherited from family members. For example, if one child in a family is diagnosed with autism, the chances increase that a sibling may also be diagnosed.

Certain factors may raise the likelihood of autism, including advanced parental age, infections during pregnancy, birth complications, having a premature baby or one with lower-than-expected fetal growth, or taking certain medications while pregnant.

Having a risk factor does not mean a child will develop autism. These factors increase susceptibility, not certainty.

Why have autism rates increased?

In the 1990s, 1 in 1,000 individuals was diagnosed with autism. Today, it’s closer to 1 in 31. The rise is largely due to greater awareness, improved screening and updated diagnostic criteria.

Clinicians are now more skilled at recognizing early signs, sometimes as early as 12 to 18 months, through play-based assessments and structured parent interviews.

Diagnostic criteria have expanded to reflect the full autism spectrum and allow for co-occurring conditions, like ADHD or intellectual disability — something that wasn’t always possible. As autism diagnoses have risen, diagnoses of other developmental disorders have declined since we now better recognize how autism presents across cognitive levels.

Increased awareness and reduced stigma have also led more families — particularly those with female children, who were historically underdiagnosed — to pursue evaluations.

How is autism diagnosed?

https://nypost.com/2025/05/12/health/why-autism-cases-have-risen-so-much-since-the-90s-and-3-common-myths-to-ignore/

Diagnosis involves a comprehensive evaluation, often with a team of specialists who focus on different aspects of brain development. Input from parents, teachers and other providers helps create a complete picture of an individual’s behavior across settings.

Partnering with your pediatrician early on is key. They can help identify early “red flags,” such as limited eye contact or reduced social smiling, as well as more subtle “pink flags,” like behavioral challenges or a stronger interest in objects rather than faces.

What are some common myths about autism?

Many myths about autism can be confusing and stressful for families. It’s important to separate fact from fiction.

One of the most harmful myths is that vaccines cause autism. Decades of research and large-scale studies have repeatedly shown that vaccines do not cause autism. Vaccines are safe and effective, and misinformation can lead to preventable diseases.

Another myth is that autism is always severe. In reality, it’s a spectrum — traits and challenges vary widely. Factors like cognitive ability, language skills, sex and co-occurring conditions such as anxiety, ADHD or depression influence how autism presents.

Symptoms can also look different in females or those with additional medical, developmental or psychiatric conditions.

Lastly, a widespread myth is that parenting causes autism. This is not true. It is a neurodevelopmental condition, not the result of any particular parenting style.

How can the symptoms of autism be supported?

Support is increasingly personalized, inclusive, neuroaffirming and evidence-based, focused on understanding each individual’s needs, respecting neurodiversity and enhancing quality of life.

There’s no one-size-fits-all approach. Effective supports may include behavioral therapies, educational accommodations and coordinated care for co-occurring conditions.

While there are no Food and Drug Administration-approved medications for core autism traits, medication can help manage related symptoms like irritability, inattention, hyperactivity, impulsivity and anxiety.

Technology, such as apps and telehealth, has expanded access to care. Early intervention remains key, but we are also increasingly focused on supporting autistic individuals throughout their lives.

Ongoing research continues to refine treatments, aiming to create empowering, supportive environments for people on the spectrum.

How to support autistic individuals

Understanding and supporting individuals with autism starts with a comprehensive developmental or neuropsychological evaluation. This can identify areas of strength and areas where additional support may be helpful.

Focusing on and building upon strengths can promote growth and well-being across all stages of life.

Family involvement is also an important part of support. When parents and caregivers learn strategies to encourage communication, adaptive skills and positive behaviors, it can strengthen relationships and create a supportive environment at home.

A range of approaches may be used to support individuals on the autism spectrum, including behavioral interventions, therapy (both individual and family-based), group programs and sometimes medication. These strategies can help address challenges and support overall development and quality of life.

*Footnote: We recognize that language preferences vary, including person-first (“individual with autism”) and identity-first (“autistic individual”) approaches. In this article, we use both respectfully, in recognition of the diverse perspectives within the autism community.

Rebecca A. Shalev, PhD, is a licensed psychologist, a board-certified behavior analyst on the Autism Spectrum Disorder Service team and a clinical associate professor within NYU Langone’s Department of Child & Adolescent Psychiatry. Kritika Nayar, PhD, is a pediatric neuropsychologist and clinical assistant professor in the same department at NYU Langone.

Carbamoyl phosphate synthetase 1 deficiency treated with personalized CRISPR gene therapy

Infant with rare, incurable disease is first to successfully receive personalized gene therapy treatment

NIH-supported gene-editing platform lays groundwork to rapidly develop treatments for other rare genetic diseases.

A research team supported by the National Institutes of Health (NIH) has developed and safely delivered a personalized gene editing therapy to treat an infant with a life-threatening, incurable genetic disease. The infant, who was diagnosed with the rare condition carbamoyl phosphate synthetase 1 (CPS1) deficiency shortly after birth, has responded positively to the treatment. The process, from diagnosis to treatment, took only six months and marks the first time the technology has been successfully deployed to treat a human patient. The technology used in this study was developed using a platform that could be tweaked to treat a wide range of genetic disorders and opens the possibility of creating personalized treatments in other parts of the body.

A team of researchers at the Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania (Penn) developed the customized therapy using the gene-editing platform CRISPR. They corrected a specific gene mutation in the baby’s liver cells that led to the disorder. CRISPR is an advanced gene editing technology that enables precise changes to DNA inside living cells. This is the first known case of a personalized CRISPR-based medicine administered to a single patient and was carefully designed to target non-reproductive cells so changes would only affect the patient.

“As a platform, gene editing -- built on reusable components and rapid customization -- promises a new era of precision medicine for hundreds of rare diseases, bringing life-changing therapies to patients when timing matters most: Early, fast, and tailored to the individual,” said Joni L. Rutter, Ph.D., director of NIH’s National Center for Advancing Translational Sciences (NCATS).

CPS1 deficiency is characterized by an inability to fully break down byproducts from protein metabolism in the liver, causing ammonia to build up to toxic levels in the body. It can cause severe damage to the brain and liver. Treatment includes a low protein diet until the child is old enough for a liver transplant. However, in this waiting period there is a risk of rapid organ failure due to stressors such as infection, trauma, or dehydration. High levels of ammonia can cause coma, brain swelling, and may be fatal or cause permanent brain damage.

The child initially received a very low dose of the therapy at six months of age, then a higher dose later. The research team saw signs that the therapy was effective almost from the start. The six-month old began taking in more protein in the diet, and the care team could reduce the medicine needed to keep ammonia levels low in the body. Another telling sign of the child’s improvement to date came after the child caught a cold, and later, had to deal with a gastrointestinal illness. Normally, such infections for a child in this condition could be extremely dangerous, especially with the possibility of ammonia reaching dangerous levels in the brain.

“We knew the method used to deliver the gene-editing machinery to the baby’s liver cells allowed us to give the treatment repeatedly. That meant we could start with a low dose that we were sure was safe,” said CHOP pediatrician Rebecca Ahrens-Nicklas, M.D., Ph.D.

“We were very concerned when the baby got sick, but the baby just shrugged the illness off,” said Penn geneticist and first author Kiran Musunuru, M.D., Ph.D. For now, much work remains, but the researchers are cautiously optimistic about the baby’s progress.

https://www.nih.gov/news-events/news-releases/infant-rare-incurable-disease-first-successfully-receive-personalized-gene-therapy-treatment

Musunuru K, Grandinette SA, Wang X, Hudson TR, Briseno K, Berry AM, Hacker JL, Hsu A, Silverstein RA, Hille LT, Ogul AN, Robinson-Garvin NA, Small JC, McCague S, Burke SM, Wright CM, Bick S, Indurthi V, Sharma S, Jepperson M, Vakulskas CA, Collingwood M, Keogh K, Jacobi A, Sturgeon M, Brommel C, Schmaljohn E, Kurgan G, Osborne T, Zhang H, Kinney K, Rettig G, Barbosa CJ, Semple SC, Tam YK, Lutz C, George LA, Kleinstiver BP, Liu DR, Ng K, Kassim SH, Giannikopoulos P, Alameh MG, Urnov FD, Ahrens-Nicklas RC. Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. N Engl J Med. 2025 May 15. doi: 10.1056/NEJMoa2504747. Epub ahead of print. PMID: 40373211.

Abstract

Base editors can correct disease-causing genetic variants. After a neonate had received a diagnosis of severe carbamoyl-phosphate synthetase 1 deficiency, a disease with an estimated 50% mortality in early infancy, we immediately began to develop a customized lipid nanoparticle-delivered base-editing therapy. After regulatory approval had been obtained for the therapy, the patient received two infusions at approximately 7 and 8 months of age. In the 7 weeks after the initial infusion, the patient was able to receive an increased amount of dietary protein and a reduced dose of a nitrogen-scavenger medication to half the starting dose, without unacceptable adverse events and despite viral illnesses. No serious adverse events occurred. Longer follow-up is warranted to assess safety and efficacy. (Funded by the National Institutes of Health and others.).

Handedness in mental and neurodevelopmental disorders

I am left-handed.

Packheiser J, Borawski J, Berretz G, Merklein SA, Papadatou-Pastou M, Ocklenburg S. Handedness in mental and neurodevelopmental disorders: A systematic review and second-order meta-analysis. Psychol Bull. 2025 Apr;151(4):476-512. doi: 10.1037/bul0000471. PMID: 40310231.

Abstract

Several meta-analyses on hand preference in mental and neurodevelopmental disorders have been published in the last decade. Some disorders, like schizophrenia, have been associated with increased rates of atypical hand preference (i.e., non-right-, left-, or mixed-hand preference)-but others, like depression, have not. To identify overarching patterns between hand preference and psychopathology and estimate the influence of potential moderators independent of diagnosis, we need to leverage rich information in the databases of these meta-analyses and conduct a higher level of analysis of meta-analytic data across diagnoses. To this end, we performed a second-order meta-analysis after reviewing, updating, and reanalyzing previously published meta-analyses on hand preference in various mental and neurodevelopmental disorders. In total, this study includes 402 data sets totaling 202,434 individuals. On average, atypical hand preference had a significantly higher frequency in cases compared to controls (nonright odds ratio [OR]: 1.46, 95% CI [1.35, 1.59]; left OR: 1.34, 95% CI [1.22, 1.48]; mixed OR: 1.63, 95% CI [1.38, 1.93]). Further analyses indicated that case-control differences varied with diagnosis. Some diagnoses, like schizophrenia, are associated with a high frequency of atypical hand preference (nonright OR: 1.50, 95% CI [1.32, 1.70]; left OR: 1.37, 95% CI [1.17, 1.61]; mixed OR: 1.70, 95% CI [1.19, 2.44]). Moderator analyses showed that neurodevelopmental conditions, nonneurodevelopmental conditions with an early age of onset, and conditions that include symptoms related to language were all associated with higher rates of atypical hand preference. This finding suggests that the association between handedness and clinical conditions is best understood from a transdiagnostic, developmental, and symptom-focused perspective.

___________________________________________________________________________

Left-handedness and certain neurological disorders could go hand-in-hand, a new study revealed, though the researchers and others acknowledged potential limitations.

While about 10% of people in the world are left-handed, people with autism are 3.5 times more likely to have the trait, according to an international team of researchers that analyzed data from over 200,000 individuals.

The study, published in the journal Psychological Bulletin, indicated that left- and mixed-handedness also appear more often in people who have diagnoses such as schizophrenia, autism and intellectual disability.

Mixed-handedness refers to a situation in which people may use their left hand for a certain task and their right hand for others, according to psychology experts.

This is slightly different from ambidexterity, which is the equal use of both hands.

"The key takeaways of this study are that alterations in hand preference from the norm (i.e., right-handedness) are associated especially with psychiatric and psychological conditions that affect the language system (e.g., dyslexia or schizophrenia) or affect neurodevelopment through an early age of onset (e.g., autism or ADHD)," lead author Dr. Julian Packheiser told Fox News Digital.

He is a researcher at the Institute of Cognitive Neuroscience at Ruhr University Bochum in Germany.

"Correlation doesn’t imply causation — and being left-handed does not mean someone will develop autism or schizophrenia."

Not all neurological conditions showed a link to people's dominant hand.

Depression and dyscalculia (a math learning disability), for example, showed no meaningful difference in hand preference compared to control groups, the study found.

Language factor

The researchers also determined that "atypical handedness" may be associated with long-term linguistic symptoms like stuttering and dyslexia.

"In most people, the dominant side of their brain is typically where speech, language, logical thought processing and hand preference is located," Dr. Earnest Lee Murray, a neurologist with West Tennessee Medical Group, told Fox News Digital.

He was not involved with the new study.

"People who are left-handed or ambidextrous often don’t have such a dominant one-sided brain — rather, the key portions of language can be divided between both sides," Murray also said.

The study also examined the likelihood of atypical handedness in clinical populations, or groups of people diagnosed with a specific set of health conditions compared to a control population.

"We suspected that left- and mixed-handedness could be associated with disorders whose symptoms are related to language," said Packheiser in a press release about the study.

"Language, like handedness, has a very one-sided location in the brain, so it stands to reason that the development of both and their disorders could be linked."

Timing is key

The researchers also considered other factors that could come into play, such as the age at which a person might exhibit symptoms.

It appears that the earlier a disorder’s symptoms emerged, the more frequently researchers saw cases of left- and mixed-handedness.

The researchers hypothesized that left- and mixed-handedness could be associated with diseases that occur very early in life, because the dominant hand is determined at a very early age – possibly even before birth.

In the womb, thumb-sucking at 10 weeks' gestation is heavily linked to which hand will be preferred later in life, they noted.

The connection could help experts potentially understand the way brains are organized and how they develop.

"The study has implications when understanding ways of finetuning the neurorehabilitation of patients with one-sided brain conditions, such as stroke, multiple sclerosis or traumatic brain injury," Murray said.

Potential limitations

Jonathan Alpert, a Manhattan-based psychotherapist and author, said the study was "interesting," though he emphasized its limitations.

"Correlation doesn’t imply causation — and being left-handed does not mean someone will develop autism or schizophrenia," Alpert, who was not involved in the study, told Fox News Digital.

"Handedness is just one of many factors that can be associated with neurological traits, and these findings should be interpreted with caution to avoid unnecessary alarm or stigma."

Alpert called for more research to understand the relationship, if any, between handedness and mental health.

Lead author Packheiser agreed the results are "purely correlational."

"We have no causal evidence that developing a psychiatric disorder linked to language or neurodevelopment causes a change in handedness, or whether changes in handedness cause any disorder," he told Fox News Digital.

"Individuals from the general public should therefore never be alarmed if their child prefers to use the left hand," the researcher said.

"But given the rise of mental disorders in the population, it is important to better understand them."

https://www.foxnews.com/health/left-handed-people-could-higher-risk-neurological-disorders-study

Chordoma

'Remarkable' results of cancer trial shared by both patient and doctor

A young Maryland woman is "relieved and recovering" after doctors performed a novel surgery to remove her potentially deadly cancerous tumors.

A surgical team at the University of Maryland Medical Center (UMMC) extracted the tumors, which had wrapped around the spinal cord, through the patient’s eye socket.

This was the first time surgeons removed a spinal tumor using a "transorbital" approach, according to a UMMC press release.

Karla Flores was just 19 when she was diagnosed with a chordoma, which is a developmental bone tumor, in her spine.

At 18, Flores started experiencing double vision, ultimately leading to her diagnosis months later.

Chordomas are very rare, with only about 300 cases occurring in the U.S. each year.

"The tumor was wrapped around the patient’s spine and spinal cord and had invaded the vertebrae in her neck, just below the base of the skull," according to Mohamed Labib, M.D., neurosurgeon at the University of Maryland Medical Center and assistant professor of neurosurgery at the University of Maryland School of Medicine.



"The primary risks were injuring the brainstem, spinal cord or major blood vessels with the drill or the fine instruments we used — any of these injuries could have resulted in paralysis or even death," Labib told Fox News Digital.

"But without surgery, the chordoma could have continued to grow and put intense pressure on the spinal cord. This, too, would have paralyzed her arms and legs and eventually killed her. So, you can see how the stakes were very high with this procedure."

The surgeons created a "huge surgical corridor" through the eye socket that enabled them to get in front of the spinal cord.

"It was a straight shot," Labib said.

"By going through the bottom of the eye socket, we were able to remove a tumor that otherwise would have been very difficult and very risky to address."


"Learning about the spinal and brain tumors was terrifying, but I am so grateful the doctors were able to remove them."

During the procedure, Labib worked with a facial plastic and reconstructive surgeon, Kalpesh T. Vakharia, M.D., who "carefully cut through the conjunctiva, the transparent membrane protecting the eye, inside the lower eyelid without disturbing the eye."

To create the pathway to the spine, Vakharia removed the bottom of Flores’ eye socket and a portion of her cheekbone, the release stated.

"We wanted to develop a surgical plan where there would be no external scars and it would be impossible to tell that the patient even had surgery," said Vakharia.

After Labib removed the tumor, Vakharia rebuilt the bottom of the eye socket using a titanium plate and rebuilt the cheek with bone from the patient’s hip, the release detailed.

"It was amazing to have had the opportunity to be part of surgery that had never been done before," Vakharia added.

This approach also prevented any damage to the eustachian tube, major blood vessels such as the jugular vein and internal carotid artery, and nerves that control swallowing and speech, Labib noted.

Prior to Flores’ surgery, Labib had the chance to practice the transorbital procedure on cadavers "many, many times."

"The fact that people are willing to donate their bodies to science enabled us to do this and saved the life of this young woman," he said.

Flores also had a large tumor around her brain stem, which was removed through two separate procedures via her skull and nose, the release stated.

The spinal tumors could have been life-threatening if they had grown to the point where they caused significant brain stem compression, according to Andrea M. Hebert, MD, a UMCC head and neck surgeon who performed the endonasal procedure and took part in the transorbital surgery.

"Many of these tumors recur, and that’s why we favor a multidisciplinary approach to treatment," said Hebert in the release.

Flores has also undergone radiation therapy to eliminate any remaining cancer cells.

"Karla is doing really well — she’s recovered from surgery and radiation and is ready to get back to work and school," Labib shared with Fox News Digital.

"She’s an incredibly brave young woman who has faced more than most her age. I expect that same strength of spirit will carry her into a promising future."

"Learning about the spinal and brain tumors was terrifying, but I am so grateful the doctors were able to remove them."

Flores does have some nerve damage due to the tumor’s proximity to the brain stem, which has caused some issues with movement of her left eye.

"Learning about the spinal and brain tumors was terrifying, but I am so grateful the doctors were able to remove them," said Flores, who plans to go to school to become a manicurist.

"I’m slowly recovering and with any problem I have, they help me," she continued.

"I keep reminding myself to take one day at a time and know that each step is an accomplishment."

Flores now plans to go to school to become a manicurist.

Looking ahead, UMMC’s team plans to demonstrate the transorbital procedure this fall to neurosurgeons from around the world, at their annual Skull Base surgery course.

"When you have such a broadened corridor to reach these tumors, you can completely remove them, which greatly reduces recurrence of the cancer," Labib told Fox News Digital.

"We also have other patients who will be receiving similar surgeries in the near future."

https://www.foxnews.com/health/rare-spinal-cancer-tumor-removed-patients-eye-university-hospital

Creatine transporter deficiency

Courtesy of my daughter.

Jeffrey Allen took home a record-breaking $10 million in prize money after winning the first season of Beast Games.

The reality competition show was inspired by Squid Game and created with YouTuber MrBeast.

Allen is using his prize money to help fund research for his son's rare disease, creatine transporter deficiency.

The winner of the first-ever Beast Games was doing it for more than just the prize money.

Before applying to the show, Jeffrey Allen started watching MrBeast YouTube videos with his son, Jack. The 9-year-old introduced his father to the videos that have already attracted 367 million subscribers on YouTube. MrBeast, whose real name is Jimmy Donaldson, has been pulling viewers into his channel for years with titles that tease reality show-like experiences and large sums of prize money.

So when Allen saw a casting advertisement for Beast Games, the Prime Video reality competition series inspired by Netflix’s Squid Game, he tells PEOPLE he knew it was going to be a big deal: “It’s MrBeast, it’s got to be huge."

And huge it was. At the start of the competition, 2,000 competitors flocked to Allegiant Stadium in Las Vegas to compete on the reality show, with only half of these competitors making it to the official Prime Video show.

“I applied for it, but I didn't really tell anybody until I knew I got in,” Allen continues. “So it was a secret I kept…  I don't wanna get anybody's hopes up and I don't want my wife to start planning what life's gonna be like with me gone for a handful of weeks. So I waited until I actually got in before I told them.”

When Beast Games was first announced, there was plenty of anticipation around its eventual premiere — especially with the record-breaking prize pool on the line. However, six months before the show's premiere, allegations of unsafe filming conditions and "chronic mistreatment" arose, with some of the eliminated contestants filing a lawsuit against Donadlson's production company and Amazon.

Despite the lawsuit, Allen claims he didn't share that same experience, stating, "My experience with MrBeast, the Beast team and then Amazon were second to none."

"The way I look at it is if you're gonna go out and compete for $5 million, it's not gonna be easy. But the conditions were more than adequate for me and my friends," Allen continues. "Honestly, I didn't know what's real and what's not... I didn't give a ton of a ton of thought to it, but I was just hoping that it didn't honestly hurt MrBeast or Amazon or the production because I had such a great time."

As a father of two sons, Allen had much more than the prize money on his mind when he decided to apply. Though he knew competing on the show would be an opportunity to let Jack “see his dad do something super cool,” he also applied hoping to use the experience as an opportunity to raise awareness for his younger son’s rare disease.

Allen’s youngest son Lucas, 7, was diagnosed with Creatine Transporter Deficiency at just 2 years old. CTD is described as “inborn errors of creatine metabolism which interrupt the formation or transport of creatine,” according to the National Organization for Rare Disorders.

“He was missing milestones, especially compared to his older brother,” Allen says of his son’s diagnosis. “He wasn't able to sit up the same way his older brother was. He wasn't able to crawl as fluidly and even the way he would eat was different.” 

Allen describes the period before they knew what was wrong as an “18-month diagnosis odyssey.”

“We strapped him up to dozens of machines, did a bunch of tests, and until almost a year and a half later, we were coming up short. There was no answers. No specialists knew what was going on, and we finally got diagnosed through an MRS,” Allen recounts.

Unfortunately, as CTD is particularly rare, there is currently no official treatment or cure for Lucas’ condition. “Our pediatrician had no clue. The specialist had no clue. And even once we were diagnosed, the geneticist to serve us from a premier academic institution had never seen a patient with his condition,” Allen says.

At the time of his application, the prize money for the first season of Beast Games was advertised to be $5 million — the most amount of money to be awarded through a reality competition to date. It wasn’t until there were only six competitors left that the stakes were upped.

“[Donaldson] wheeled out another pyramid of $5 million and says, 'If you want, someone can grab this coin and flip a coin. And if you call it right, everybody will compete for 10 million. If you don't, you're eliminated and you get to compete for 5 million,’“ Allen recalls. “My friend Gage — number 974 who's an absolute, amazing man — grabbed that coin, flipped it, called it right and we all competed for $10 million.”

For Allen, the “ultimate goal” was to take home the prize money to help his son. “I need to take care of him," he says. "I want to make sure he's taken care of at home, but also, can we invest into research to help ultimately find a treatment for him and other kids like him?”

Allen is a volunteer board member of the Association for Creatine Deficiencies, a parent-led organization aimed at finding and supporting research to help those with CTD and two other cerebral creatine deficiency syndromes. He says this is the “primary funder” for such research, and with the prize money officially in his hands, his next goal is to find projects to put the winnings toward, while also making sure measures are put in place to take care of Lucas.

“My goal is to help my son, and that means, how do I make sure that he's taken care of in case mom and dad pass away? 'Cause right now he'd have to live with us forever. How do I make sure that his brother doesn't have to care for him as he ages?” Allen explains. “We look at how do we care for Lucas at home? And then how do we care for other Lucases around the world?”

“The last thing we want to do is put the burden on an association that doesn't have the projects to fund,” he continues. “So our job is to help source these projects, whether they're academic or whether they're private. We want to invest into treatments that are gonna help Lucas and help kids like Lucas.”

The win is two-fold for Allen. Not only does he have the finances to better Lucas’ quality of life, but the experience was an immense bonding experience with Jack, who he said was his "Beast Games coach.”

“It's one thing to experience it and you think you remember how it went. But it's a whole other thing to watch the show and see other people's perspective,” he explains. “It was so fun to watch with my son Jack… He taught me everything about MrBeast and all of his videos.”

Winning Beast Games has also allowed Allen to put his career in healthcare sales and entrepreneurship on hold to focus on other ways to raise money for CTD research. His next mission is to ruck across California, walking weights for 365 miles from Death Valley to the California coast, “representing the 365 days a year that Lucas and other CTD kiddos suffer with this condition.”

Allen and other participants in his challenge will be sharing content on Instagram and YouTube as they make the journey, using their platforms to further raise awareness for cerebral creatine deficiency syndromes. But before leaving, Jack has requested he and his dad rewatch all 10 episodes of Beast Games from the beginning.

“Winning $10 million is gonna help Lucas and kids like Lucas tremendously. And to actually fund a treatment, you need tens of millions of dollars. So I'm not gonna be able to do it alone. We need a ton of support, but it's a great start,” Allen says.

“Over the course of the next coming years, we'll have some larger projects that we would never have been able to fund if it wasn't for MrBeast and Beast Games.”

https://people.com/beast-games-winner-shares-heartwarming-use-for-10-million-prize-exclusive-11686523

See: https://childnervoussystem.blogspot.com/2015/11/cerebral-creatine-deficiency-syndrome-1.html