التفاصيل البيبلوغرافية
| العنوان: |
Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases |
| المؤلفون: |
Maas, R. R., Iwanicka-Pronicka, K., Kalkan Ucar, S., Alhaddad, B., AlSayed, M., Al-Owain, M. A., Al-Zaidan, H. I., Balasubramaniam, S., Barić, I., Bubshait, D. K., Burlina, A., Christodoulou, J., Chung, W. K., Colombo, R., Darin, Niklas, 1964, Freisinger, P., Garcia Silva, M. T., Grunewald, S., Haack, T. B., van Hasselt, P. M., Hikmat, O., Hörster, F., Isohanni, P., Ramzan, K., Kovacs-Nagy, R., Krumina, Z., Martin-Hernandez, E., Mayr, J. A., McClean, P., De Meirleir, L., Naess, K., Ngu, L. H., Pajdowska, M., Rahman, S., Riordan, G., Riley, L., Roeben, B., Rutsch, F., Santer, R., Schiff, M., Seders, M., Sequeira, S., Sperl, W., Staufner, C., Synofzik, M., Taylor, R. W., Trubicka, J., Tsiakas, K., Unal, O., Wassmer, E., Wedatilake, Y., Wolff, T., Prokisch, H., Morava, E., Pronicka, E., Wevers, R. A., de Brouwer, A. P., Wortmann, S. B. |
| المصدر: |
Annals of Neurology. 82(6):1004-1015 |
| مصطلحات موضوعية: |
Neurology, Neurologi, 3 methylglutaconic acid, lactic acid, carboxylesterase, SERAC1 protein, human, 3 methylglutaconic aciduria dystonia deafness hepatopathy encephalopathy Leigh like syndrome, aciduria, adolescent, adult, Article, basal ganglion, brain disease, child, clinical feature, communication skill, differential diagnosis, disease course, dyskinesia, dystonia, epilepsy, female, gene, gene mutation, genetic variability, hearing impairment, human tissue, hypersalivation, hypoglycemia, incidence, infant, intellectual impairment, intelligence, lactate blood level, lactic acidosis, Leigh disease, liver disease, liver dysfunction, liver failure, major clinical study, multicenter study, muscle biopsy, muscle hypotonia, neuroimaging, neuroradiology, newborn, newborn disease, nuclear magnetic resonance imaging, optic nerve atrophy, perception deafness, phenotype, priority journal, prognosis, putamen, serac1 gene, spasticity, speech development, survival, tongue disease, visual impairment, walking, amino acid sequence, clinical trial, cohort analysis, deafblindness, diagnostic imaging, disease exacerbation, genetics, male, mutation, preschool child, young adult, Carboxylic Ester Hydrolases, Child, Preschool, Cohort Studies, Deaf-Blind Disorders, Disease Progression, Humans, Infant, Newborn, Intellectual Disability, Optic Atrophy |
| الوصف: |
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. © 2017 American Neurological Association |
| URL الوصول: |
https://gup.ub.gu.se/publication/264592 |
| قاعدة البيانات: |
SwePub |