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Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases
Annals of neurology, 2017-12, Vol.82 (6), p.1004-1015
2017

Details

Autor(en) / Beteiligte
Titel
Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases
Ist Teil von
  • Annals of neurology, 2017-12, Vol.82 (6), p.1004-1015
Ort / Verlag
United States: Wiley Subscription Services, Inc
Erscheinungsjahr
2017
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • Objective 3‐Methylglutaconic aciduria, dystonia–deafness, hepatopathy, encephalopathy, Leigh‐like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. Methods This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. Results Sixty‐seven individuals (39 previously unreported) from 59 families were included (age range = 5 days–33.4 years, median age = 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset = 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy‐nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic “putaminal eye” was seen in 53%. The urinary marker 3‐methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. Interpretation MEGDHEL syndrome is a progressive deafness–dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004–1015
Sprache
Englisch
Identifikatoren
ISSN: 0364-5134, 1531-8249
eISSN: 1531-8249
DOI: 10.1002/ana.25110
Titel-ID: cdi_swepub_primary_oai_prod_swepub_kib_ki_se_137244001
Format
–
Schlagworte
3 methylglutaconic acid, 3 methylglutaconic aciduria dystonia deafness hepatopathy encephalopathy Leigh like syndrome, Aciduria, Adolescent, Adult, Age, Amino Acid Sequence, Auditory defects, Basal ganglia, basal ganglion, brain disease, carboxylesterase, Carboxylic Ester Hydrolases, Carboxylic Ester Hydrolases - genetics, Child, Child, Preschool, clinical feature, clinical trial, Cochlea, Cochlear implants, cohort analysis, Cohort Studies, communication skill, Deaf-Blind Disorders, Deaf-Blind Disorders - diagnostic imaging, Deaf-Blind Disorders - genetics, Deaf-Blind Disorders - therapy, deafblindness, Deafness, diagnostic imaging, differential diagnosis, disease course, disease exacerbation, Disease Progression, dyskinesia, Dystonia, Dystonia - diagnostic imaging, Dystonia - genetics, Dystonia - therapy, Encephalopathy, epilepsy, Female, Ganglia, gene, gene mutation, genetic variability, genetics, Hearing aids, hearing impairment, Hearing loss, human, human tissue, Humans, hypersalivation, Hypoglycemia, Hypotonia, Implants, incidence, Infant, Infant, Newborn, Intellectual Disability, Intellectual Disability - diagnostic imaging, Intellectual Disability - genetics, Intellectual Disability - therapy, intellectual impairment, intelligence, lactate blood level, lactic acid, lactic acidosis, Leigh disease, Leigh-like syndrome, Liver, liver disease, Liver diseases, liver dysfunction, liver failure, Magnetic resonance imaging, major clinical study, Male, Medicin och hälsovetenskap, multicenter study, muscle biopsy, muscle hypotonia, Mutation, Mutation - genetics, Neonates, neuroimaging, Neurologi, Neurology, neuroradiology, newborn, newborn disease, nuclear magnetic resonance imaging, Optic Atrophy, Optic Atrophy - diagnostic imaging, Optic Atrophy - genetics, Optic Atrophy - therapy, optic nerve atrophy, perception deafness, phenotype, Preschool, preschool child, priority journal, prognosis, putamen, Saliva, serac1 gene, SERAC1 protein, Spasticity, speech development, survival, tongue disease, visual impairment, walking, Young Adult

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