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

BACKGROUND: Recessive mutations in the 3-hydroxyisobutyryl-CoA hydrolasegene (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 disorderand MRI features suggestive of Leigh syndrome. METHODS: Clinical and metabolic assessment was followed by autozygosity mapping and whole exomeand Sanger sequencing. HIBCH enzyme activity and the bioenergeticprofile were determined in patient fibroblasts. RESULTS: The movement disorderwas dominated by ataxia in one family and by dystoniain 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.