Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases.

Autor:	Maas RR; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., Iwanicka-Pronicka K; Department of Audiology and Phoniatrics, Children's Memorial Health Institute, Warsaw, Poland., Kalkan Ucar S; Division of Metabolic Disease, Ege University Medical Faculty, Department of Pediatrics, Izmir, Turkey., Alhaddad B; Institute of Human Genetics, Technische UniversitätMünchen, Munich, Germany., AlSayed M; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Al-Owain MA; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Al-Zaidan HI; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Balasubramaniam S; Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia.; Discipline of Genetic Medicine & Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia., Barić I; Department of Pediatrics, University Hospital Center, Zagreb, Croatia.; School of Medicine, University of Zagreb, Zagreb, Croatia., Bubshait DK; Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia., Burlina A; Division of Inherited Metabolic Diseases, Department of Pediatrics, University Hospital of Padua, Padua, Italy., Christodoulou J; Neurodevelopmental Genomics Research Group, Murdoch Children's Research Institute, and Department of Paediatrics, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia.; Genetic Metabolic Disorders Research Unit and Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia.; Discipline of Child and Adolescent Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia., Chung WK; Departments of Pediatrics and Medicine, Columbia University, New York, NY., Colombo R; Institute of Clinical Biochemistry, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.; Center for the Study of Rare Hereditary Diseases, Niguarda Ca' Granda Metropolitan Hospital, Milan, Italy., Darin N; Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Queen Silvia's Children's Hospital, Gothenburg, Sweden., Freisinger P; Childrens Hospital, Klinikum Reutlingen, Reutlingen, Germany., Garcia Silva MT; Inborn Errors of Metabolism and Mitochondrial Disease Unit, '12 de Octubre' University Hospital, Avenida de Cordoba sn, 28041 Madrid, Spain. Rare Diseases Biomedical Research Centre (CIBERER), Madrid, Spain.; Complutense University, Madrid, Spain., Grunewald S; Metabolic Medicine Department, Great Ormond Street Hospital for Children National Health Service Foundation Trust, University College London Institute of Child Health, London, United Kingdom., Haack TB; Institute of Human Genetics, Technische UniversitätMünchen, Munich, Germany.; Institute of Medical Genetics and Applied Genomics, Tübingen, Germany., van Hasselt PM; Wilhelmina Children's Hospital Utrecht, University Medical Center Utrecht, Utrecht, the Netherlands., Hikmat O; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway., Hörster F; Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany., Isohanni P; Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland., Ramzan K; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Kovacs-Nagy R; Institute of Human Genetics, Technische UniversitätMünchen, Munich, Germany., Krumina Z; Department of Biology and Microbiology, Riga Stradin's University, Riga, Latvia., Martin-Hernandez E; Inborn Errors of Metabolism and Mitochondrial Disease Unit, '12 de Octubre' University Hospital, Avenida de Cordoba sn, 28041 Madrid, Spain. Rare Diseases Biomedical Research Centre (CIBERER), Madrid, Spain.; Complutense University, Madrid, Spain., Mayr JA; Department of Pediatrics, Salzburg State Hospitals and Paracelsus Medical University, Salzburg, Austria., McClean P; Leeds Teaching Hospitals National Health Service Trust, Leeds, United Kingdom., De Meirleir L; Pediatric Neurology, Brussels University Hospital, Brussels, Belgium., Naess K; Department of Pediatric Neurology, Karolinska University Hospital, Stockholm, Sweden., Ngu LH; Division of Clinical Genetics, Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia., Pajdowska M; Department of Clinical Biochemistry, Radioimmunology, and Experimental Medicine, Children's Memorial Health Institute, Warsaw, Poland., Rahman S; University College London Great Ormond Street Institute of Child Health, London, United Kingdom., Riordan G; Department of Pediatric Neurology, Red Cross War Memorial Children's Hospital, Cape Town, South Africa., Riley L; Genetic Metabolic Disorders Research Unit and Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia.; Discipline of Child and Adolescent Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia., Roeben B; Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany., Rutsch F; Department of General Pediatrics, Münster University Children's Hospital, Münster, Germany., Santer R; Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany., Schiff M; Reference Center for Inherited Metabolic Diseases, AP-HP, Robert Debré Hospital, University Paris Diderot-Sorbonne Paris Cité, Paris, France AND INSERM U1141, Paris, France., Seders M; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands., Sequeira S; Metabolic Unit, Dona Estefânia Hospital, Lisbon, Portugal., Sperl W; Department of Pediatrics, Salzburg State Hospitals and Paracelsus Medical University, Salzburg, Austria., Staufner C; Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany., Synofzik M; Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany., Taylor RW; Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom., Trubicka J; Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland., Tsiakas K; Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany., Unal O; Division of Metabolic Diseases, Hacettepe University Children's Hospital, Ankara, Turkey., Wassmer E; Birmingham Children's Hospital, Birmingham, United Kingdom., Wedatilake Y; University College London Great Ormond Street Institute of Child Health, London, United Kingdom., Wolff T; Nottingham University Hospitals National Health Service Trust, Nottingham Children's Hospital, Nottingham, United Kingdom., Prokisch H; Institute of Human Genetics, Technische UniversitätMünchen, Munich, Germany.; Institute of Human Genetics, Helmholtz Center Munich, Neuherberg, Germany., Morava E; Hayward Genetics Center and Department of Pediatrics, Tulane University Medical School, New Orleans, LA., Pronicka E; Department of Pediatrics, Nutrition and Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland., Wevers RA; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., de Brouwer AP; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.; Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands., Wortmann SB; Institute of Human Genetics, Technische UniversitätMünchen, Munich, Germany.; Department of Pediatrics, Salzburg State Hospitals and Paracelsus Medical University, Salzburg, Austria.; Institute of Human Genetics, Helmholtz Center Munich, Neuherberg, Germany.
Jazyk:	angličtina
Zdroj:	Annals of neurology [Ann Neurol] 2017 Dec; Vol. 82 (6), pp. 1004-1015.
DOI:	10.1002/ana.25110
Abstrakt:	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. (© 2017 American Neurological Association.)
Databáze:	MEDLINE
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