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

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dc.contributor.authorCollaborators
dc.contributor.authorKrumina, Zita
dc.contributor.institutionDepartment of Biology and Microbiology
dc.date.accessioned2021-09-01T08:45:01Z
dc.date.available2021-09-01T08:45:01Z
dc.date.issued2017-12
dc.descriptionFunding Information: M.S. was supported by the Else Kröner-Fresenius Stiftung” This study was supported by the German Bundesministerium für Bildung und Forschung (BMBF) and Horizon2020 through the E-Rare project GENOMIT (01GM1603 and 01GM1207 for HP and FWF I 2741-B26 for J.A.M. J.A.M., S.B.W., W.S. were supported by the Vereinigung zur Förderung Pädiatrischer Forschung und Fortbildung Salzburg. R.W.T. was supported by the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), the Medical Research Council (MRC) Centre for Translational Research in Neuromuscular Disease, Mitochondrial Disease Patient Cohort (UK) (G0800674), the Lily Foundation and the UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children. Funding Information: M.S. was supported by the Else Kr€oner-Fresenius Stiftung” This study was supported by the German Bun-desministerium fu€r Bildung und Forschung (BMBF) and Horizon2020 through the E-Rare project GENOMIT (01GM1603 and 01GM1207 for HP and FWF I 2741-B26 for J.A.M. J.A.M., S.B.W., W.S. were supported by the Vereinigung zur F€orderung P€adiatrischer Forschung und Fortbildung Salzburg. R.W.T. was supported by the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), the Medical Research Council (MRC) Centre for Translational Research in Neuromuscular Disease, Mitochondrial Disease Patient Cohort (UK) (G0800674), the Lily Foundation and the UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children. Publisher Copyright: © 2017 American Neurological Association
dc.description.abstractObjective: 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.en
dc.description.statusPeer reviewed
dc.format.extent12
dc.format.extent2965092
dc.identifier.citationCollaborators & Krumina, Z 2017, 'Progressive deafness–dystonia due to SERAC1 mutations : A study of 67 cases', Annals of Neurology, vol. 82, no. 6, pp. 1004-1015. https://doi.org/10.1002/ana.25110
dc.identifier.doi10.1002/ana.25110
dc.identifier.issn0364-5134
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/6146
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85038411692&partnerID=8YFLogxK
dc.identifier.urlhttps://onlinelibrary.wiley.com/doi/10.1002/ana.25110
dc.language.isoeng
dc.relation.ispartofAnnals of Neurology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3.2 Clinical medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectNeurology
dc.subjectClinical Neurology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleProgressive deafness–dystonia due to SERAC1 mutations : A study of 67 casesen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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