TY - JOUR
T1 - A movement disorder with dystonia and ataxia caused by a mutation in the HIBCH gene
AU - Schottmann, Gudrun
AU - Sarpong, Akosua
AU - Lorenz, Carmen
AU - Weinhold, Natalie
AU - Gill, Esther
AU - Teschner, Lisa
AU - Ferdinandusse, Sacha
AU - Wanders, Ronald J. A.
AU - Prigione, Alessandro
AU - Schuelke, Markus
PY - 2016
Y1 - 2016
N2 - 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. 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. 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. 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
AB - 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. 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. 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. 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
U2 - https://doi.org/10.1002/mds.26704
DO - https://doi.org/10.1002/mds.26704
M3 - Article
C2 - 27400804
SN - 0885-3185
VL - 31
SP - 1733
EP - 1739
JO - Movement disorders
JF - Movement disorders
IS - 11
ER -