Maas, Roeltje R; Iwanicka-Pronicka, Katarzyna; Kalkan Ucar, Sema; Alhaddad, Bader; AlSayed, Moeenaldeen; Al-Owain, Mohammed A; Al-Zaidan, Hamad I; Balasubramaniam, Shanti; Bari?, 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; Kovacs-Nagy, Reka; Krumina, Zita; Martin-Hernandez, 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, René; 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     «

Maas, Roeltje R; Iwanicka-Pronicka, Katarzyna; Kalkan Ucar, Sema; Alhaddad, Bader; AlSayed, Moeenaldeen; Al-Owain, Mohammed A; Al-Zaidan, Hamad I; Balasubramaniam, Shanti; Bari?, 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; Kovacs-Nagy, Reka; Krumina, Z...     »

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.     «

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, includ...     »