title: 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease.
abstract: We describe three patients, from two Spanish families, with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency, a recently described X-linked neurodegenerative inborn error of isoleucine metabolism. Two of them are males with severe lactic acidosis suggestive of a mitochondrial encephalopathy, and the third is a female who was less severely affected, suggesting skewed X-inactivation. Molecular studies revealed a new missense mutation, 740A-->G, in one family and a previously described mutation, 388C-->T, in the other, causing the amino acid substitutions N247S and R130C, respectively. Both male patients died, one of them despite treatment with an isoleucine-restricted diet, but the disease has remained stable in the female patient after 1 y of treatment.
authors.affiliation: Institut de Bioquímica, Corporaciò Sanitària Cláinic, Edifici Helios III, 08028 Barcelona, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Perez-Cerda
authors.forename: Judit
authors.initials: J
authors.lastname: García-Villoria
authors.forename: Rob
authors.initials: R
authors.lastname: Ofman
authors.forename: Pedro Ruiz
authors.initials: PR
authors.lastname: Sala
authors.forename: Begoña
authors.initials: B
authors.lastname: Merinero
authors.forename: Julio
authors.initials: J
authors.lastname: Ramos
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: García-Silva
authors.forename: Beatriz
authors.initials: B
authors.lastname: Beseler
authors.forename: Jaime
authors.initials: J
authors.lastname: Dalmau
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ugarte
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases; D000429:Alcohol Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000378:metabolism*; D002648:Child; D041321:Chromosomes, Human, X; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007532:Isoleucine / Q000378:metabolism*; D008297:Male; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000378:metabolism*
chemical_list: D007532:Isoleucine; D000429:Alcohol Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C419903:2-methyl-3-hydroxybutyryl-coenzyme A dehydrogenase