Holocarboxylase synthetase deficiency: a biotin-responsive organic acidemia

J Pediatr. 1980 May;96(5):845-9. doi: 10.1016/s0022-3476(80)80554-3.


The clinical and biochemical features of an infant affected by holocarboxylase synthetase deficiency are presented. The patient was the sibling of the deceased child in whose cultured skin fibroblasts the precise enzymatic disorder was first determined. This fact permitted administration of specific therapy in the form of oral biotin, resulting in immediate improvement from impending respiratory failure and shock. The clinical response to biotin was accompanied by recovery of the biochemical mechanisms known to be biotin-dependent, as manifested by disappearance of intermediates in urine and blood. The variability of biotin responsiveness and the diversity of clinical presentation in the patients originally thought to have a deficiency of beta methylcrotonylCoA carboxylase, a biotin-dependent enzyme, raises the question of a separate, specific apocarboxylase defect.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / drug therapy
  • Amino Acid Metabolism, Inborn Errors / etiology*
  • Amino Acids / blood
  • Amino Acids / cerebrospinal fluid
  • Apoproteins / deficiency
  • Apoproteins / metabolism
  • Biotin / deficiency
  • Biotin / metabolism
  • Biotin / therapeutic use*
  • Carbon-Nitrogen Ligases*
  • Chromatography, Ion Exchange
  • Humans
  • Infant
  • Infant, Newborn
  • Ligases / deficiency*
  • Ligases / metabolism
  • Renal Aminoacidurias / etiology*


  • Amino Acids
  • Apoproteins
  • Biotin
  • Ligases
  • Carbon-Nitrogen Ligases
  • holocarboxylase synthetases