Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases
Makaleler > Tam Makale · 2017
Yazarlar: Roeltje R. Maas, Katarzyna Iwanicka‐Pronicka, Sema KALKAN UÇAR, Bader Alhaddad, Moeenaldeen AlSayed, Mohammed Al‐Owain, Hamad Alzaidan, Shanti Balasubramaniam, Ivo Barić, Dalal Bubshait, Alberto Burlina, John Christodoulou, Wendy K. Chung, Roberto Colombo, Niklas Darín, Peter Freisinger, Maria Teresa Garcia Silva, Stephanie Grünewald, Tobias B. Haack, Peter M. van Hasselt, Omar Hikmat, Friederike Hörster, Pirjo Isohanni, Khushnooda Ramzan, Réka Kovács-Nagy, Zita Krūmiņa, Elena Martín‐Hernández, Johannes A. Mayr, Patricia McClean, Linda De Meırleır, K Naess, Lock Hock Ngu, Magdalena Pajdowska, Shamima Rahman, Gillian Riordan, Lisa G. Riley, Benjamin Röeben, Frank Rutsch, René Santer, Manuel Schiff, Martine Seders, Sílvia Sequeira, Wolfgang Sperl, Christian Staufner, Matthis Synofzik, Robert W. Taylor, Joanna Trubicka, Konstantinos Tsiakas, Özlem Ünal, Evangeline Wassmer, Yehani Wedatilake, Toni Wolff, Holger Prokisch, Éva Morava, Ewa Pronicka, Ron A. Wevers, Arjan Pm de Brouwer, Saskia B. Wortmann
Greater South Information System, Uluslararası, 2017
DOI: 10.60692/ff7e0-b0608
Özet
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.