Identification of HIBCH Gene Mutations Causing Autosomal Recessive Leigh Syndrome: A Gene Involved in Valine Metabolism

• Published in: Pediatric neurology 2015-03, Vol.52 (3), p.361-365
• Main Authors: Soler-Alfonso, Claudia, MD, Enns, Gregory M., MB, ChB, Koenig, Mary Kay, MD, Saavedra, Heather, RD, LD, Bonfante-Mejia, Eliana, MD, Northrup, Hope, MD
• Format: Article
• Language: English
• Subjects: Brain - pathology; Child, Preschool; Family Health; Female; HIBCH; Humans; inborn error of metabolism; Leigh Disease - genetics; Leigh syndrome; Magnetic Resonance Imaging; Mutation - genetics; Neurology; Pediatrics; Thiolester Hydrolases - genetics; valine; Valine - genetics; whole exome sequencing
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2014.10.023

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. Patient and 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.