Maas Roeltje R, Iwanicka-Pronicka Katarzyna, Kalkan Ucar Sema, Alhaddad Bader, AlSayed Moeenaldeen, Al-Owain Mohammed A, Al-Zaidan 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, 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 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
Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Audiology and Phoniatrics, Children's Memorial Health Institute, Warsaw, Poland.
Ann Neurol. 2017 Dec;82(6):1004-1015. doi: 10.1002/ana.25110.
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 - 甲基戊二酸尿症、肌张力障碍 - 耳聋、肝病、脑病、类 Leigh 综合征（MEGDHEL）由 SERAC1 基因双等位基因突变引起。
这项多中心研究探讨了各器官系统的疾病进程。报告了代谢、神经放射学和遗传学研究结果。
纳入了来自59个家庭的67名个体（39名此前未报告）（年龄范围 = 5天至33.4岁，中位年龄 = 9岁）。共鉴定出41种不同的 SERAC1 变体，其中20种此前未被报告。除2个表型较轻的家庭外，所有受影响个体均表现出显著一致的表型和病程。超过40%的病例出现严重、可逆的新生儿肝功能障碍和低血糖。中位年龄6个月时开始出现肌张力减退（91%），随后是进行性痉挛（82%，中位发病年龄 = 15个月）和肌张力障碍（82%，18个月）。大多数受影响个体从未学会走路（68%）。79%的患者有听力损失，58%从未学会说话，几乎所有患者都有严重智力残疾（88%）。磁共振成像特征相应地较为一致，双侧基底神经节受累（98%）；53%的患者可见特征性的“壳核眼”。几乎所有患者（98%）尿中均有3 - 甲基戊二酸尿标志物。支持性治疗主要针对痉挛和流涎，对接受治疗的个体有效；助听器或人工耳蜗并未改善沟通能力。
MEGDHEL 综合征是一种进行性耳聋 - 肌张力障碍综合征，常伴有新生儿肝脏受累且病程可逆，疾病进程显著一致。《神经病学纪事》2017年；82:1004 - 1015。
