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Key Features

  • Isolated pyruvate carboxylase deficiency presents with lactic acidosis and hyperammonemia in early infancy

  • Even if biochemically stabilized, the neurologic outcome is dismal

  • Isolated 3-methylcrotonyl-CoA carboxylase deficiency

    • Frequently recognized on newborn screening using acylcarnitine analysis

    • Usually a benign condition that sometimes causes symptoms of acidosis and neurologic depression

Clinical Findings

  • Holocarboxylase synthetase deficiency usually presents in neonates with hypotonia, skin problems, and massive acidosis

  • Biotinidase deficiency presents later with a syndrome of ataxia, seizures, seborrhea, and alopecia

  • Mental retardation, hearing loss, and optic nerve atrophy can develop in untreated patients

  • Newborn screening is justified because the neurologic sequelae of the disorder in many patients are preventable if treated early


  • Diagnosis should be considered in patients with typical symptoms or in those with primary lactic acidosis

  • Urine organic acids are usually but not always abnormal

  • Diagnosis is made by enzyme assay of carboxylase activities in fibroblasts or leucocytes

  • Biotinidase can be assayed in serum

  • Holocarboxylase synthetase can be assayed in leukocytes or fibroblasts


  • Oral administration of pharmacologic doses of biotin reverses the organic aciduria within days and the clinical symptoms within days to weeks

  • Hearing loss can occur in patients with profound biotinidase deficiency despite treatment

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