Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: evidence of alpha-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial beta-oxidation

J Inherit Metab Dis. 1987;10(4):367-75. doi: 10.1007/BF01799979.

Abstract

In addition to the previously reported abnormalities, urine extracts from three cases of succinic semialdehyde dehydrogenase deficiency have shown consistently increased amounts of 2,4-dihydroxybutyric acid, and its lactone, and 3-hydroxypropionic acid, metabolites related to the alpha-oxidation of 4-hydroxybutyric acid. Threo- and erythro-4,5-dihydroxyhexanoic acids have also been identified for the first time and probably arise from the reaction of succinic semialdehyde with an intermediate in the pyruvate dehydrogenase pathway. Adipic acid excretion is also consistently raised, suggesting secondary interference with mitochondrial beta-oxidation. The presence of these metabolites could be a source of diagnostic confusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipates / urine
  • Carboxylic Acids / urine*
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Hydroxybutyrate Dehydrogenase / deficiency*
  • Hydroxybutyrates / urine
  • Infant
  • Oxidation-Reduction
  • Propionates / urine
  • Pyruvate Dehydrogenase Complex / metabolism
  • gamma-Aminobutyric Acid / analogs & derivatives
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Adipates
  • Carboxylic Acids
  • Hydroxybutyrates
  • Propionates
  • Pyruvate Dehydrogenase Complex
  • gamma-Aminobutyric Acid
  • adipic acid
  • Hydroxybutyrate Dehydrogenase
  • 4-hydroxybutyrate dehydrogenase
  • propionic acid
  • succinic semialdehyde