2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease.
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.
Perez-Cerda
Celia
C
Institut de Bioquímica, Corporaciò Sanitària Cláinic, Edifici Helios III, 08028 Barcelona, Spain.
García-Villoria
Judit
J
Ofman
Rob
R
Sala
Pedro Ruiz
PR
Merinero
Begoña
B
Ramos
Julio
J
García-Silva
Maria Teresa
MT
Beseler
Beatriz
B
Dalmau
Jaime
J
Wanders
Ronald J A
RJ
Ugarte
Magdalena
M
Ribes
Antonia
A
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*
D007532:Isoleucine; D000429:Alcohol Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C419903:2-methyl-3-hydroxybutyryl-coenzyme A dehydrogenase