title: A movement disorder with dystonia and ataxia caused by a mutation in the HIBCH gene.
abstract: 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.
authors.affiliation: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schottmann
authors.affiliation: Sozialpädiatrisches Zentrum Neuropädiatrie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Akosua
authors.initials: A
authors.lastname: Sarpong
authors.affiliation: Max Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Lorenz
authors.affiliation: Sozialpädiatrisches Zentrum Stoffwechsel, Charité-Universitätsmedizin, Berlin, German.
authors.forename: Natalie
authors.initials: N
authors.lastname: Weinhold
authors.affiliation: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Gill
authors.affiliation: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Teschner
authors.affiliation: Department of Clinical Chemistry and Pediatrics, Emma Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sacha
authors.initials: S
authors.lastname: Ferdinandusse
authors.affiliation: Department of Clinical Chemistry and Pediatrics, Emma Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.affiliation: Max Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Prigione
authors.affiliation: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000503:physiopathology*; D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000503:physiopathology*; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology; D002648:Child; D020821:Dystonic Disorders / Q000235:genetics / Q000503:physiopathology; D005260:Female; D006801:Humans; D007888:Leigh Disease / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009069:Movement Disorders / Q000235:genetics / Q000503:physiopathology*; D020125:Mutation, Missense; D010375:Pedigree; D013869:Thiolester Hydrolases / Q000172:deficiency* / Q000235:genetics; D055815:Young Adult
chemical_list: D013869:Thiolester Hydrolases; C035908:3-hydroxyisobutyryl-CoA hydrolase
keywords: HIBCH gene; Leigh syndrome; ataxia; basal ganglia necrosis; dystonia; valine metabolism