Rapid differential diagnosis of carboxylase deficiencies and evaluation for biotin-responsiveness in a single blood sample

Clin Chim Acta. 1985 Jan 30;145(2):151-62. doi: 10.1016/0009-8981(85)90282-7.


We have developed a method for rapid differential diagnosis of isolated or multiple deficiencies of the 3 mitochondrial biotin-dependent carboxylases: propionyl-CoA (PCC), 3-methylcrotonyl-CoA (MCC) and pyruvate carboxylase (PC), and for simultaneous evaluation of biotin-responsiveness using a single blood sample. Lymphocytes were isolated from heparinized blood and preincubated without and with 10(-5) mol/l biotin in medium before determination of PCC, MCC and PC activities. Plasma was used for estimation of biotin concentration and biotinidase activity. A definitive diagnosis could be made in 7 of 9 patients studied up to now: 4 patients suffered from biotin-nonresponsive isolated PCC-deficiency, and 3 patients from biotin-responsive multiple carboxylase deficiency caused by deficient biotinidase activity. In two patients, a carboxylase deficiency was excluded. These results were confirmed in studies using fibroblasts. In addition, a simple method for detection of deficiency in holocarboxylase synthesis is described.

MeSH terms

  • Acyl Coenzyme A / blood
  • Acyl Coenzyme A / deficiency
  • Adult
  • Amidohydrolases / blood
  • Biotin*
  • Biotinidase
  • Carbon-Carbon Ligases*
  • Carbon-Nitrogen Ligases*
  • Cells, Cultured
  • Child, Preschool
  • Diagnosis, Differential
  • Fibroblasts / enzymology
  • Humans
  • Infant
  • Ligases / antagonists & inhibitors
  • Ligases / blood
  • Ligases / deficiency*
  • Lymphocytes / enzymology
  • Pyruvate Carboxylase / blood
  • Pyruvate Carboxylase Deficiency Disease


  • Acyl Coenzyme A
  • propionyl-coenzyme A
  • Biotin
  • Amidohydrolases
  • Biotinidase
  • Ligases
  • Carbon-Nitrogen Ligases
  • holocarboxylase synthetases
  • Carbon-Carbon Ligases
  • Pyruvate Carboxylase
  • methylcrotonoyl-CoA carboxylase