2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease

Pediatr Res. 2005 Sep;58(3):488-91. doi: 10.1203/01.pdr.0000176916.94328.cd.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases
  • Alcohol Oxidoreductases / deficiency
  • Alcohol Oxidoreductases / genetics*
  • Amino Acid Metabolism, Inborn Errors / enzymology
  • Amino Acid Metabolism, Inborn Errors / metabolism*
  • Child
  • Chromosomes, Human, X*
  • Female
  • Genetic Linkage*
  • Humans
  • Infant
  • Infant, Newborn
  • Isoleucine / metabolism*
  • Male
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / metabolism*


  • Isoleucine
  • Alcohol Oxidoreductases
  • 3-Hydroxyacyl CoA Dehydrogenases
  • 2-methyl-3-hydroxybutyryl-coenzyme A dehydrogenase