The Pino family said they need help raising funds for training a service dog for Maddie to help when she's battling an episode of paralysis or epilepsy brought on by AHC.
"It is a disorder which combines really multiple disorders together," Duke Children's Hospital Dr. Mohamad A. Mikati said. He added that children with AHC suffer from reoccurring episodes of paralysis, epilepsy, painful stiffening, and attention deficit hyperactive disorder...
He's also Maddie's doctor, and Maddie's dad, Jason, said their family moved from their home in Beaufort, S.C. to Durham in 2013 to be closer to Mikati and Duke Children's Hospital.
Maddie's mother, Landis Pino, biggest fears come when she wonders about Maddie's future.
"Are we going to see her grow up to be a teenager? Are we going to see her reach other milestones? Or are we going to be planning events that no parent should have to plan," she said.
The Pino family is hoping to train their dog Lucy to be a service dog for Maddie, so Lucy can alert them if Maddie is having an episode - giving them time to administer medication if it's an epileptic episode, or providing support for her if it's an episode of paralysis.
Landis Pino said Lucy is already a big help to the family in detecting episodes.
"She'll be sitting there, and she'll just start barking and when you turn and look, Maddie will be in an episode," Landis said.
She said training Lucy would take some of the burden off of the family's shoulders. They recently found out their 2 year-old daughter, Marley Pino, has AHC too.
"It's severe enough to deal with one child who has that. These are two siblings that have it," Dr. Mikati said. "So I can imagine how stressful it can be on the family."
Dr. Mikati said episodes of paralysis in children who have AHC can alternate from one side of their body to the other, and episodes can last anywhere from minutes to hours, days, or even weeks.
http://abc11.com/health/durham-family-battles-one-in-a-million-disease/965645/
Jaffer F, Avbersek A, Vavassori R, Fons C, Campistol J, Stagnaro M, De Grandis
ReplyDeleteE, Veneselli E, Rosewich H, Gianotta M, Zucca C, Ragona F, Granata T, Nardocci N, Mikati M, Helseth AR, Boelman C, Minassian BA, Johns S, Garry SI, Scheffer IE,
Gourfinkel-An I, Carrilho I, Aylett SE, Parton M, Hanna MG, Houlden H, Neville B,
Kurian MA, Novy J, Sander JW, Lambiase PD, Behr ER, Schyns T, Arzimanoglou A, Cross JH, Kaski JP, Sisodiya SM. Faulty cardiac repolarization reserve in
alternating hemiplegia of childhood broadens the phenotype. Brain. 2015 Aug 21.
pii: awv243. [Epub ahead of print]
Abstract
Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable.
Heinzen EL, Arzimanoglou A, Brashear A, Clapcote SJ, Gurrieri F, Goldstein DB,
ReplyDeleteJóhannesson SH, Mikati MA, Neville B, Nicole S, Ozelius LJ, Poulsen H, Schyns T,
Sweadner KJ, van den Maagdenberg A, Vilsen B; ATP1A3 Working Group. Distinct
neurological disorders with ATP1A3 mutations. Lancet Neurol. 2014 May;13(5):503-14.
Abstract
Genetic research has shown that mutations that modify the protein-coding sequence of ATP1A3, the gene encoding the α3 subunit of Na(+)/K(+)-ATPase, cause both rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood. These discoveries link two clinically distinct neurological diseases to the same gene, however, ATP1A3 mutations are, with one exception, disease-specific. Although the exact mechanism of how these mutations lead to disease is still unknown, much knowledge has been gained about functional consequences of ATP1A3 mutations using a range of in-vitro and animal model systems, and the role of Na(+)/K(+)-ATPases in the brain. Researchers and clinicians are attempting to further characterise neurological manifestations associated with mutations in ATP1A3, and to build on the existing molecular knowledge to understand how specific mutations can lead to different diseases.
Sasaki M, Ishii A, Saito Y, Morisada N, Iijima K, Takada S, Araki A, Tanabe Y,
ReplyDeleteArai H, Yamashita S, Ohashi T, Oda Y, Ichiseki H, Hirabayashi S, Yasuhara A,
Kawawaki H, Kimura S, Shimono M, Narumiya S, Suzuki M, Yoshida T, Oyazato Y,
Tsuneishi S, Ozasa S, Yokochi K, Dejima S, Akiyama T, Kishi N, Kira R, Ikeda T,
Oguni H, Zhang B, Tsuji S, Hirose S. Genotype-phenotype correlations in
alternating hemiplegia of childhood. Neurology. 2014 Feb 11;82(6):482-90.
Abstract
OBJECTIVE:
Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype-phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC.
METHODS:
Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study. ATP1A3 mutations were analyzed using Sanger sequencing. Detailed clinical information was collected from family members of patients with AHC and clinicians responsible for their care.
RESULTS:
Gene analysis revealed 33 patients with de novo heterozygous missense mutations of ATP1A3: Glu815Lys in 12 cases (36%), Asp801Asn in 10 cases (30%), and other missense mutations in 11 cases. Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Statistical analysis revealed significant differences in the history of neonatal onset, gross motor level, status epilepticus, and respiratory paralysis in the Glu815Lys group compared with the other groups. In addition, 8 patients who did not receive flunarizine had severe motor deteriorations.
CONCLUSIONS:
The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.
Mikati MA, Maguire H, Barlow CF, Ozelius L, Breakefield XO, Klauck SM, Korf B,
ReplyDeleteO'Tuama SL, Dangond F. A syndrome of autosomal dominant alternating hemiplegia: clinical presentation mimicking intractable epilepsy; chromosomal studies; and physiologic investigations. Neurology. 1992 Dec;42(12):2251-7.
Abstract
We report the familial occurrence and apparent autosomal dominant inheritance of alternating hemiplegia of childhood. The proband, a 9-year-old boy, presented with developmental retardation, rare tonic-clonic seizures, and frequent episodes of flaccid alternating hemiplegia that had been presumed to represent postictal paralysis. The hemiplegia spells, which started in his first year, did not respond to multiple antiepileptics. Between attacks, there was choreoathetosis and dystonic posturing. Father, brother, paternal uncle, and paternal grandmother had similar histories of alternating hemiplegia. Investigations included negative CT, metabolic, and coagulation studies. EEG and SPECT 99mTc exametazime scanning failed to reveal any significant slowing or any major changes in cortical perfusion during hemiplegia as compared with nonhemiplegic periods. The karyotype revealed a balanced reciprocal translocation, 46,XY,t(3;9)(p26;q34) in the patient, in all the affected living relatives, and in one apparently unaffected sibling. The asymptomatic mother had a normal karyotype. Analysis of DNA markers was consistent with the karyotype results. Both affected siblings were treated with and responded to flunarizine therapy, with a greater than 70% decrease in attack frequency. Documented flunarizine trough serum concentrations were 28.9 ng/ml in the proband and 6.6 ng/ml in his brother.