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A movement disorder with dystonia and ataxia caused by a mutation in the HIBCH gene
Author(s) -
Schottmann Gudrun,
Sarpong Akosua,
Lorenz Carmen,
Weinhold Natalie,
Gill Esther,
Teschner Lisa,
Ferdinandusse Sacha,
Wanders Ronald J. A.,
Prigione Alessandro,
Schuelke Markus
Publication year - 2016
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26704
Subject(s) - dystonia , ataxia , movement disorders , choreoathetosis , exome sequencing , sanger sequencing , mutation , medicine , genetics , disease , biology , gene , psychiatry
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. © 2016 International Parkinson and Movement Disorder Society