Maas, RR;
Iwanicka-Pronicka, K;
Ucar, SK;
Alhaddad, B;
AlSayed, M;
Al-Owain, MA;
Al-Zaidan, HI;
... Wortmann, SB; + view all
(2017)
Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases.
Annals of Neurology
, 82
(6)
pp. 1004-1015.
10.1002/ana.25110.
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Abstract
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
| Type: | Article |
|---|---|
| Title: | Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/ana.25110 |
| Publisher version: | http://doi.org/10.1002/ana.25110 |
| Language: | English |
| Additional information: | Copyright © 2017 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10049490 |
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