Premium
Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases
Author(s) -
Maas Roeltje R.,
IwanickaPronicka Katarzyna,
Kalkan Ucar Sema,
Alhaddad Bader,
AlSayed Moeenaldeen,
AlOwain Mohammed A.,
AlZaidan Hamad I.,
Balasubramaniam Shanti,
Barić Ivo,
Bubshait Dalal K.,
Burlina Alberto,
Christodoulou John,
Chung Wendy K.,
Colombo Roberto,
Darin Niklas,
Freisinger Peter,
Garcia Silva Maria Teresa,
Grunewald Stephanie,
Haack Tobias B.,
van Hasselt Peter M.,
Hikmat Omar,
Hörster Friederike,
Isohanni Pirjo,
Ramzan Khushnooda,
KovacsNagy Reka,
Krumina Zita,
MartinHernandez Elena,
Mayr Johannes A.,
McClean Patricia,
De Meirleir Linda,
Naess Karin,
Ngu Lock H.,
Pajdowska Magdalena,
Rahman Shamima,
Riordan Gillian,
Riley Lisa,
Roeben Benjamin,
Rutsch Frank,
Santer Rene,
Schiff Manuel,
Seders Martine,
Sequeira Silvia,
Sperl Wolfgang,
Staufner Christian,
Synofzik Matthis,
Taylor Robert W.,
Trubicka Joanna,
Tsiakas Konstantinos,
Unal Ozlem,
Wassmer Evangeline,
Wedatilake Yehani,
Wolff Toni,
Prokisch Holger,
Morava Eva,
Pronicka Ewa,
Wevers Ron A.,
de Brouwer Arjan P.,
Wortmann Saskia B.
Publication year - 2017
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25110
Subject(s) - dystonia , medicine , spasticity , pediatrics , hypotonia , physical therapy , psychiatry
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