SORD hereditary neuropathy

I may have this. (update 5/21/22 I do have this)

Cortese A, Zhu Y, Rebelo AP, Negri S, Courel S, Abreu L, Bacon CJ, Bai Y, Bis-Brewer DM, Bugiardini E, Buglo E, Danzi MC, Feely SME, Athanasiou-Fragkouli A, Haridy NA; Inherited Neuropathy Consortium; Isasi R, Khan A, Laurà M, Magri S, Pipis M, Pisciotta C, Powell E, Rossor AM, Saveri P, Sowden JE, Tozza S, Vandrovcova J, Dallman J, Grignani E, Marchioni E, Scherer SS, Tang B, Lin Z, Al-Ajmi A, Schüle R, Synofzik M, Maisonobe T, Stojkovic T, Auer-Grumbach M, Abdelhamed MA, Hamed SA, Zhang R, Manganelli F, Santoro L, Taroni F, Pareyson D, Houlden H, Herrmann DN, Reilly MM, Shy ME, Zhai RG, Zuchner S. Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4. Erratum in: Nat Genet. 2020 Jun;52(6):640. PMID: 32367058; PMCID: PMC8353599.

Erratum in Author Correction: 

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S, Courel S, Abreu L, Bacon CJ, Bai Y, Bis-Brewer DM, Bugiardini E, Buglo E, Danzi MC, Feely SME, Athanasiou-Fragkouli A, Haridy NA; Inherited Neuropathy Consortium; Isasi R, Khan A, Laurà M, Magri S, Pipis M, Pisciotta C, Powell E, Rossor AM, Saveri P, Sowden JE, Tozza S, Vandrovcova J, Dallman J, Grignani E, Marchioni E, Scherer SS, Tang B, Lin Z, Al-Ajmi A, Schüle R, Synofzik M, Maisonobe T, Stojkovic T, Auer-Grumbach M, Abdelhamed MA, Hamed SA, Zhang R, Manganelli F, Santoro L, Taroni F, Pareyson D, Houlden H, Herrmann DN, Reilly MM, Shy ME, Zhai RG, Zuchner S.Nat Genet. 2020 Jun;52(6):640. doi: 10.1038/s41588-020-0649-7.PMID: 32457452

Abstract

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes.

Encephalocele

 https://www.youtube.com/watch?v=gMOSs6WuwYU

The downside of having an almost perfect memory

 The Downside of Having an Almost Perfect Memory 

Joey DeGrandis is one of fewer than 100 people identified to have Highly Superior Autobiographical Memory, or HSAM. 

  

Joey DeGrandis was about 10 years old when his parents first realized there was something special about his memory. “Someone would mention an event from years ago that we’d done as a family, and I’d casually say, ‘Oh, that was a Monday,’ or ‘that happened on June 20,’” says DeGrandis, who is now 33. “My mom would cross-reference it with old calendars she’d kept, and they were a little dumbfounded at how accurate I was.”   

DeGrais showed off his skill that year at show at school, wowing his audience by correctly identifying the day of the week for any given date in recent history. And for the next 15 years or so, DeGrandis thought of his talent mostly as a neat party trick: not something everyone could do, but not something with much significance, either. He would later find that there are upsides—and surprising downsides—to having an almost perfect memory. 

In 2010, when DeGrandis was 26, he saw a segment on 60 Minutes featuring a handful of people with a similar ability: a condition now known as highly superior autobiographical memory, or HSAM. “I was on a road trip with a friend and ended up in California, and I decided to go visit this doctor who was studying these people who seemed to be like me,” he says. 

Identifying a rare ability 

That doctor was James McGaugh, a research professor in neurobiology and behavior at the University of California, Irvine. McGaugh began studying HSAM in 2000, after a young woman named Jill Price contacted him about her memory “problem.”  

 

Price, who would later become the first person to be diagnosed with HSAM, had complained that her extraordinary memory was a burden. “Whenever I see a date flash on the television (or anywhere else for that matter) I automatically go back to that day and remember where I was, what I was doing, what day it fell on and on and on and on and on,” she had written in an email to McGaugh. “It is non-stop, uncontrollable, and totally exhausting.” 

By 2010, McGaugh and his colleagues had identified a few others with an uncanny ability to link calendar dates with events, both major news (like the Challenger explosion or Princess Diana’s death) and mundane personal details (like what they ate or what song they heard on the radio). After appearing on 60 Minutes, McGaugh received more than 600 emails and phone calls from people—like DeGrandis—who thought they might also have this ability. 

Ultimately, only about 60 of those people were identified by McGaugh and his team as actually having HSAM. Even in the years since, and even with plenty of additional media coverage, less than 100 people have been diagnosed with the condition. “That shows you how rare it is,” says McGaugh, “that millions of people have heard about this, and yet we can only find a tiny number who fit the criteria.” 

The pros and cons of never forgetting 

 

DeGrandis, being one of those people, now participates in ongoing studies by McGaugh and other memory researchers. (In his everyday life, he works in marketing—in a job that has nothing to do with his special ability, he says.) He has enjoyed meeting others with HSAM and has been struck by the things they have in common. 

DeGrandis says he’s struggled from depression and anxiety, which he believes may be linked to his inability to let certain things go. In getting to know other HSAM study participants, he’s learned this is a common theme. 

“I consider myself lucky in that I’ve had a pretty good life, so I have a lot of happy, warm and fuzzy memories I can think back on,” he says. “But I do tend to dwell on things longer than the average person, and when something painful does happen, like a break-up or the loss of a family member, I don’t forget those feelings.” 

Research also suggests that people with HSAM tend to have obsessive traits. “Some subjects, like Price, focused on orderliness,” McGaugh wrote in Learning and Memory: A Comprehensive Reference, which was updated this year to include a chapter on HSAM. “Some were germ-avoidant, and some had hobbies that involved intense, focused and sustained efforts,” he added. It’s not known yet whether these traits are the result of their superior memory, or if both are caused by another underlying factor. 

And while people with superior memories have an uncanny talent for linking dates and events, they do occasionally make mistakes. “Their memories are much more detailed than ours, and last for a longer period of time, but they’re still not video recordings,” says McGaugh. “Memory is a distracting process, and what we pull from our brains isn’t always entirely accurate.” 

People with HSAM are also no better than normal when it comes to remembering things like faces or phone numbers. The ability is not the same as a so-called photographic memory, which allows people to vividly recall details from a scene they’ve only observed for a short time; nor is it the same as a talent held by competitive “memory athletes” who use mnemonic devices to remember long strings of data, for example. 

“I’m not great with names, or with mundane details like whether I brushed my teeth today or where I put my keys,” says DeGrandis. “My mind is always moving and filled with so many other things, and maybe that contributes, ironically, to a poorer short-term memory.” 

What science can learn from people with superior memories 

 

Nearly two decades after identifying the first case of HSAM, there’s still a lot researchers don’t know about the condition. But there have been a lot of gains, as well. 

“We now have a set of twins in the study, one who has this ability and one who doesn’t,” says McGaugh. “We also have a number of younger people—one as young as 8—with the ability. This proves that it’s not just present in mature adults, and it’s not something that is learned and rehearsed over time.” 

The UC Irvine researchers also plan to conduct functional MRI scans on people in the HSAM study to see if their brains work differently while they are retrieving information. “I have colleagues in Rome who have started this functional imaging,” says McGaugh, “and we have some evidence that there are real differences we can hopefully learn a lot from.” Previous research using non-functional MRIs—which only depict anatomical structures and not active processes like blood flow—has already shown some basic structural differences between the brains of people with and without HSAM. 

McGaugh says that understanding the neurobiology behind HSAM may provide new insights into how the brain stores and retrieves memories. It may even be useful in the fight against Alzheimer’s disease and other forms of dementia and memory loss, he says, although it’s too soon to definitively say if or how. 

As for DeGrandis, he’s happy to lend his mind to science in the hopes that it will ultimately help people who have trouble remembering things—not forgetting them. And while he and others like him sometimes feel burdened by this special talent, DeGrandis is ultimately glad to have it. “It can be frustrating, but it’s also really wonderful to have easy access to happy memories,” he says. “I really try not to take that for granted.” 

https://time.com/5045521/highly-superior-autobiographical-memory-hsam/