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A movement disorder with dystonia and ataxia caused by a mutation in the HIBCH gene

Item Type:Article
Title:A movement disorder with dystonia and ataxia caused by a mutation in the HIBCH gene
Creators Name:Schottmann, G. and Sarpong, A. and Lorenz, C. and Weinhold, N. and Gill, E. and Teschner, L. and Ferdinandusse, S. and Wanders, R.J.A. and Prigione, A. and Schuelke, M.
Abstract:BACKGROUND: Recessive mutations in the 3-hydroxyisobutyryl-CoA hydrolase gene (HIBCH) are associated with a rare neurodegenerative disease that affects the basal ganglia. Most patients die during infancy or early childhood. Here we describe 5 adolescent and adult patients from 2 unrelated families, who presented with a movement disorder and MRI features suggestive of Leigh syndrome. METHODS: Clinical and metabolic assessment was followed by autozygosity mapping and whole exome and Sanger sequencing. HIBCH enzyme activity and the bioenergetic profile were determined in patient fibroblasts. RESULTS: The movement disorder was dominated by ataxia in one family and by dystonia in the other. All affected family members carried the identical homozygous c.913A>G (p.T305A) HIBCH mutation. Enzyme activity was reduced, and a valine challenge reduced the oxygen consumption rate. CONCLUSIONS: We report the first adult patients with HIBCH deficiency and a disease course much milder than previously reported, thereby expanding the HIBCH-associated phenotypic spectrum.
Keywords:HIBCH Gene, Ataxia, Dystonia, Basal Ganglia Necrosis, Valine Metabolism, Leigh Syndrome
Source:Movement Disorders
Page Range:1733-1739
Date:November 2016
Official Publication:https://doi.org/10.1002/mds.26704
PubMed:View item in PubMed

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