Phytanic acid alpha-oxidation: accumulation of 2-hydroxyphytanic acid and absence of 2-oxophytanic acid in plasma from patients with peroxisomal disorders

J Lipid Res. 1992 Oct;33(10):1449-57.

Abstract

A stable isotope dilution method was developed for the measurement of 2-hydroxyphytanic acid and 2-oxophytanic acid in plasma. In plasma from healthy individuals and from patients with Refsum's disease, 2-hydroxyphytanic acid was found at levels less than 0.2 mumol/l, whereas the acid accumulated in plasma from patients with rhizomelic chondrodysplasia punctata, generalized peroxisomal dysfunction, and a single peroxisomal beta-oxidation enzyme deficiency. In plasma from both healthy controls and patients with peroxisomal disorders, 2-oxophytanic acid was undetectable. Four different groups of diseases were characterized with a defective phytanic acid alpha-oxidation and/or pristanic acid beta-oxidation: 1) Refsum's disease, with a defect at phytanic acid alpha-hydroxylation; 2) rhizomelic chondrodysplasia punctata, with a defect at 2-hydroxyphytanic acid decarboxylation; 3) generalized peroxisomal disorders, with defects at 2-hydroxyphytanic acid decarboxylation and at pristanic acid beta-oxidation; 4) single peroxisomal beta-oxidation enzyme deficiencies, with a defect at pristanic acid beta-oxidation, resulting in an impaired phytanic acid alpha-oxidation by inhibition. The results indicate that 2-hydroxyphytanic acid decarboxylation and pristanic acid beta-oxidation take place in peroxisomes.

MeSH terms

  • Adolescent
  • Adult
  • Carbon Radioisotopes
  • Child
  • Child, Preschool
  • Fatty Acids / blood
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Phytanic Acid / analogs & derivatives*
  • Phytanic Acid / blood
  • Phytanic Acid / metabolism*
  • Refsum Disease / blood*
  • Refsum Disease / metabolism

Substances

  • Carbon Radioisotopes
  • Fatty Acids
  • Phytanic Acid
  • 2-hydroxyphytanic acid
  • 2-oxophytanic acid
  • pristanic acid