title: Identification of HIBCH gene mutations causing autosomal recessive Leigh syndrome: a gene involved in valine metabolism.
abstract: BACKGROUND
  Leigh syndrome is a progressive neurodegenerative disorder with usual onset of symptoms during the first year of life. The disorder has been associated with mutations in over 30 genes. This difficulty with genetic heterogeneity makes whole exome sequencing a more cost-effective approach for investigation of etiology.
  
  
  RESULTS
  We describe an individual with typical Leigh syndrome who was found to have compound heterozygous mutations in the gene HIBCH (3-hydroxyisobutyryl coenzyme A hydrolase), an enzyme involved in the catabolism of valine. She exhibited significant clinical improvement after a valine-restricted diet.
  
  
  CONCLUSIONS
  A subset of patients with uncharacterized Leigh syndrome present with specific biochemical abnormalities. This report highpoints the challenges and restrictions of routine metabolic testing and features the recognition of inborn errors of metabolism as potential treatable causes of Leigh syndrome.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Texas Health Science Center at Houston, Houston, Texas. Electronic address: claudiarsoler@gmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Soler-Alfonso
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Lucile Packard Children's Hospital, Stanford University, Stanford, California.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Enns
authors.affiliation: Department of Pediatrics, Division of Child and Adolescent Neurology, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Koenig
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Heather
authors.initials: H
authors.lastname: Saavedra
authors.affiliation: Department of Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Eliana
authors.initials: E
authors.lastname: Bonfante-Mejia
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Hope
authors.initials: H
authors.lastname: Northrup
mesh_terms: D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006801:Humans; D007888:Leigh Disease / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D009154:Mutation / Q000235:genetics*; D013869:Thiolester Hydrolases / Q000235:genetics*; D014633:Valine / Q000235:genetics*
chemical_list: D013869:Thiolester Hydrolases; D014633:Valine
keywords: HIBCH; Leigh syndrome; inborn error of metabolism; valine; whole exome sequencing