Beta-ketothiolase deficiency is a defect of mitochondrial acetoacetyl-CoA thiolase (T2) involving ketone body metabolism and isoleucine catabolism. This new rare disorder is characterized by normal early development followed by a progressive loss of mental and motor skills. It is clinically characterized by intermittent ketoacidotic episodes, with no clinical symptoms between episodes. Ketoacidotic episodes are usually severe and sometimes accompanied by lethargy/coma. Some patients may have neurologicalimpairments as a sequela of these episodes. The disorder is caused by a mutation in a gene localized to chromosome region 11q and is transmitted in an autosomal recessive manner. More than 20 mutations have been identified. T2 deficiency is characterized by urinary excretion of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate, and tiglylglycine but its extent is variable. Acylcarnitine analysis is also useful for the diagnosis. However, the diagnosis should be confirmed by enzyme assay. Treatments of acute episodes include infusion of sufficient glucose and correction of acidosis. Fundamental management includes mild protein restriction and prophylactic glucose infusion during mild illness. This disorder has usually a favorable outcome. Clinical consequences can be avoided by early diagnosis, appropriate management of ketoacidosis, and modest protein restriction.
Last update: September 2004