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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, N.* ; Freisinger, P.* ; Garcia Silva, M.T.* ; Grunewald, S.* ; Haack, T.B.* ; van Hasselt, P.M.* ; Hikmat, O.* ; Hörster, F.* ; Isohanni, P.* ; Ramzan, K.* ; Kovács-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.* ; Röeben, 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.

Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases.

Ann. Neurol. 82, 1004-1015 (2017)
Verlagsversion DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Megdel Syndrome; 3-methylglutaconic Aciduria; Mitochondrial Dysfunction; Gene; Encephalopathy; Biosynthesis; Deficiency; Phenotype; Phospholipids; Management
ISSN (print) / ISBN 0364-5134
e-ISSN 1531-8249
Zeitschrift Annals of Neurology
Quellenangaben Band: 82, Heft: 6, Seiten: 1004-1015 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken