Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate

Ayesha Ahmad, Stephen G. Kahler, Priya S. Kishnani, Merce Artigas-Lopez, Anuradha S. Pappu, Robert Steiner, David S. Millington, Johan L.K. Van Hove

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


A patient with severe pyruvate carboxylase deficiency presented at age 11 weeks with metabolic decompensation after routine immunization. She was comatose, had severe lactic acidemia (22 mM) and ketosis, low aspartate and glutamate, elevated citrulline and proline, and mild hyperammonemia. Head magnetic resonance imaging showed subdural hematomas and mild generalized brain atrophy. Biotin-unresponsive pyruvate carboxylase deficiency was diagnosed. To provide oxaloacetate, she was treated with high-dose citrate (7.5 mol/kg-1/day-1), aspartate (10 mmol/kg-1/day-1), and continuous drip feeding. Lactate and ketones diminished dramatically, and plasma amino acids normalized, except for arginine, which required supplementation. In the cerebrospinal fluid (CSF), glutamine remained low and lysine elevated, showing the treatment had not normalized brain chemistry. Metabolic decompensations, triggered by infections or fasting, diminished after the first year. They were characterized by severe lactic and ketoacidosis, hypernatremia, and a tendency to hypoglycemia. At age 3 1/2 years she has profound mental retardation, spasticity, and grand mal and myoclonic seizures only partially controlled by anticonvulsants. The new treatment regimen has helped maintain metabolic control, but the neurological outcome is still poor.

Original languageEnglish (US)
Pages (from-to)331-338
Number of pages8
JournalAmerican Journal of Medical Genetics
Issue number4
StatePublished - 1999
Externally publishedYes


  • Anaplerotic role
  • Aspartate
  • Citrate
  • Neurological outcome
  • Pyruvate carboxylase
  • Treatment

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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