Propionyl-CoA carboxylase deficiency: case report, effect of low-protein diet and identification of 3-oxo-2-methylvaleric acid 3-hydroxy-2-methylvaleric acid, and maleic acid in urine

Scand J Clin Lab Invest. 1981 Apr;41(2):117-26. doi: 10.3109/00365518109092023.


Vomiting, lethargy and metabolic acidosis were the main initial symptoms of metabolic disease in a 1 month old girl. Her older sister had died from a similar disease, considered to be Reye's syndrome, at an age of 15 months. The urine of the present case contained 2-methylcitric acid, 3-hydroxypropionic acid, N-propionylglycine, 2-hydroxy-3-methylbutyric acid, N-tiglylglycine, 3-hydroxyvaleric acid and glutaric acid. These metabolites are all known to be associated with propionyl-CoA accumulation. Free propionic acid was not detected in the urine. In addition, the urine contained 3-oxo-2-methylvaleric acid and 3-hydroxy-2-methylvaleric acid, probably formed by condensation of two molecules of propionyl-CoA. The identity of these metabolites was confirmed by synthesis. An elevated urinary concentration of maleic acid and fumaric acid was another constant abnormality. The activity of propionyl-CoA carboxylase in leucocytes was about 20% of the normal activity. The girl was teated with a low-protein diet since the diagnosis was made at an age of 1 month, and her psychomotor development was satisfactory at an age of 2 1/2 years. She had a few episodes of acidosis during infections.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / diet therapy
  • Amino Acid Metabolism, Inborn Errors / genetics
  • Amino Acid Metabolism, Inborn Errors / metabolism*
  • Biotin / administration & dosage
  • Caproates / urine
  • Carboxy-Lyases / deficiency*
  • Dietary Proteins / therapeutic use*
  • Female
  • Humans
  • Hydroxy Acids / urine*
  • Infant
  • Infant, Newborn
  • Keto Acids / urine*
  • Leukocytes / enzymology
  • Maleates / urine*
  • Methylmalonyl-CoA Decarboxylase
  • Pentanoic Acids / urine*
  • Propionates / blood
  • Propionates / deficiency
  • Reye Syndrome / diagnosis
  • Valerates / urine*


  • 3-keto-2-methylvaleric acid
  • Caproates
  • Dietary Proteins
  • Hydroxy Acids
  • Keto Acids
  • Maleates
  • Pentanoic Acids
  • Propionates
  • Valerates
  • 4-hydroxyhexanoic acid
  • 3-hydroxy-2-methylvaleric acid
  • Biotin
  • maleic acid
  • Carboxy-Lyases
  • Methylmalonyl-CoA Decarboxylase