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

作者：Schottmann Gudrun; Sarpong Akosua; Lorenz Carmen; Weinhold Natalie; Gill Esther; Teschner Lisa; Ferdinandusse Sacha; Wanders Ronald J A; Prigione Alessandro; Schuelke Markus

来源：Movement Disorders, 2016, 31(11): 1733-1739.

DOI：10.1002/mds.26704

• HIBCH gene
• ataxia
• dystonia
• basal ganglia necrosis
• valine metabolism
• Leigh syndrome

BackgroundRecessive 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.
MethodsClinical 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.
ResultsThe 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.
ConclusionsWe report the first adult patients with HIBCH deficiency and a disease course much milder than previously reported, thereby expanding the HIBCH-associated phenotypic spectrum.

• 出版日期2016-11