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Progressive Deafness-Dystonia due to SERAC1 Mutations: A Study of 67 cases

2017-12Journal article Open access
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dc.contributor.authorMaas, RR
dc.contributor.authorIwanicka-Pronicka, K
dc.contributor.authorKalkan Ucar, S
dc.contributor.authorAlhaddad, B
dc.contributor.authorAlSayed, M
dc.contributor.authorAl-Owain, MA
dc.contributor.authorAl-Zaidan, HI
dc.contributor.authorBalasubramaniam, S
dc.contributor.authorBarić, I
dc.contributor.authorBubshait, DK
dc.contributor.authorBurlina, A
dc.contributor.authorChristodoulou, J
dc.contributor.authorChung, WK
dc.contributor.authorColombo, R
dc.contributor.authorDarin, N
dc.contributor.authorFreisinger, P
dc.contributor.authorGarcia Silva, MT
dc.contributor.authorGrunewald, S
dc.contributor.authorHaack, TB
dc.contributor.authorvan Hasselt, PM
dc.contributor.authorHikmat, O
dc.contributor.authorHörster, F
dc.contributor.authorIsohanni, P
dc.contributor.authorRamzan, K
dc.contributor.authorKovacs-Nagy, R
dc.contributor.authorKrumina, Z
dc.contributor.authorMartin-Hernandez, E
dc.contributor.authorMayr, JA
dc.contributor.authorMcClean, P
dc.contributor.authorDe Meirleir, L
dc.contributor.authorNaess, K
dc.contributor.authorNgu, LH
dc.contributor.authorPajdowska, M
dc.contributor.authorRahman, S
dc.contributor.authorRiordan, G
dc.contributor.authorRiley, L
dc.contributor.authorRoeben, B
dc.contributor.authorRutsch, F
dc.contributor.authorSanter, R
dc.contributor.authorSchiff, M
dc.contributor.authorSeders, M
dc.contributor.authorSequeira, S
dc.contributor.authorSperl, W
dc.contributor.authorStaufner, C
dc.contributor.authorSynofzik, M
dc.contributor.authorTaylor, RW
dc.contributor.authorTrubicka, J
dc.contributor.authorTsiakas, K
dc.contributor.authorUnal, O
dc.contributor.authorWassmer, E
dc.contributor.authorWedatilake, Y
dc.contributor.authorWolff, T
dc.contributor.authorProkisch, H
dc.contributor.authorMorava, E
dc.contributor.authorPronicka, E
dc.contributor.authorWevers, RA
dc.contributor.authorde Brouwer, AP
dc.contributor.authorWortmann, SB
dc.date.accessioned2019-03-13T13:38:26Z
dc.date.available2019-03-13T13:38:26Z
dc.date.issued2017-12
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;82:1004-1015pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAnn Neurol. 2017 Dec;82(6):1004-1015pt_PT
dc.identifier.doi10.1002/ana.25110pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3195
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley and Sonspt_PT
dc.subjectAdolescentpt_PT
dc.subjectAdultpt_PT
dc.subjectAmino Acid Sequencept_PT
dc.subjectCarboxylic Ester Hydrolasespt_PT
dc.subjectChildpt_PT
dc.subjectChild, Preschoolpt_PT
dc.subjectCohort Studiespt_PT
dc.subjectDeaf-Blind Disorderspt_PT
dc.subjectDystoniapt_PT
dc.subjectFemalept_PT
dc.subjectHumanspt_PT
dc.subjectInfantpt_PT
dc.subjectInfant, Newbornpt_PT
dc.subjectIntellectual Disabilitypt_PT
dc.subjectMalept_PT
dc.subjectMutationpt_PT
dc.subjectOptic Atrophypt_PT
dc.subjectYoung Adultpt_PT
dc.subjectDisease Progressionpt_PT
dc.subjectHDE MTBpt_PT
dc.titleProgressive Deafness-Dystonia due to SERAC1 Mutations: A Study of 67 casespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1015pt_PT
oaire.citation.issue6pt_PT
oaire.citation.startPage1004-1015pt_PT
oaire.citation.volume82pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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