RT Journal Article
T1 Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases.
A1 Maas, Roeltje R
A1 Iwanicka-Pronicka, Katarzyna
A1 Kalkan Ucar, Sema
A1 Alhaddad, Bader
A1 AlSayed, Moeenaldeen
A1 Al-Owain, Mohammed A
A1 Al-Zaidan, Hamad I
A1 Balasubramaniam, Shanti
A1 Barić, Ivo
A1 Bubshait, Dalal K
A1 Burlina, Alberto
A1 Christodoulou, John
A1 Chung, Wendy K
A1 Colombo, Roberto
A1 Darin, Niklas
A1 Freisinger, Peter
A1 Garcia Silva, Maria Teresa
A1 Grunewald, Stephanie
A1 Haack, Tobias B
A1 van Hasselt, Peter M
A1 Hikmat, Omar
A1 Hörster, Friederike
A1 Isohanni, Pirjo
A1 Ramzan, Khushnooda
A1 Kovacs-Nagy, Reka
A1 Krumina, Zita
A1 Martin-Hernandez, Elena
A1 Mayr, Johannes A
A1 McClean, Patricia
A1 De Meirleir, Linda
A1 Naess, Karin
A1 Ngu, Lock H
A1 Pajdowska, Magdalena
A1 Rahman, Shamima
A1 Riordan, Gillian
A1 Riley, Lisa
A1 Roeben, Benjamin
A1 Rutsch, Frank
A1 Santer, Rene
A1 Schiff, Manuel
A1 Seders, Martine
A1 Sequeira, Silvia
A1 Sperl, Wolfgang
A1 Staufner, Christian
A1 Synofzik, Matthis
A1 Taylor, Robert W
A1 Trubicka, Joanna
A1 Tsiakas, Konstantinos
A1 Unal, Ozlem
A1 Wassmer, Evangeline
A1 Wedatilake, Yehani
A1 Wolff, Toni
A1 Prokisch, Holger
A1 Morava, Eva
A1 Pronicka, Ewa
A1 Wevers, Ron A
A1 de Brouwer, Arjan P
A1 Wortmann, Saskia B
AB 3-Methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. 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. 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.
YR 2017
FD 2017
LK http://hdl.handle.net/10668/11876
UL http://hdl.handle.net/10668/11876
LA en
DS RISalud
RD Apr 7, 2025