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

Publication ,  Journal Article
Ahmad, A; Kahler, SG; Kishnani, PS; Artigas-Lopez, M; Pappu, AS; Steiner, R; Millington, DS; Van Hove, JL
Published in: Am J Med Genet
December 3, 1999

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.

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Published In

Am J Med Genet

DOI

ISSN

0148-7299

Publication Date

December 3, 1999

Volume

87

Issue

4

Start / End Page

331 / 338

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Pyruvate Carboxylase Deficiency Disease
  • Lactic Acid
  • Ketosis
  • Intellectual Disability
  • Infant
  • Humans
  • Follow-Up Studies
  • Female
  • Dose-Response Relationship, Drug
 

Citation

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Ahmad, A., Kahler, S. G., Kishnani, P. S., Artigas-Lopez, M., Pappu, A. S., Steiner, R., … Van Hove, J. L. (1999). Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. Am J Med Genet, 87(4), 331–338. https://doi.org/10.1002/(sici)1096-8628(19991203)87:4<331::aid-ajmg10>3.0.co;2-k
Ahmad, A., S. G. Kahler, P. S. Kishnani, M. Artigas-Lopez, A. S. Pappu, R. Steiner, D. S. Millington, and J. L. Van Hove. “Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate.Am J Med Genet 87, no. 4 (December 3, 1999): 331–38. https://doi.org/10.1002/(sici)1096-8628(19991203)87:4<331::aid-ajmg10>3.0.co;2-k.
Ahmad A, Kahler SG, Kishnani PS, Artigas-Lopez M, Pappu AS, Steiner R, et al. Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. Am J Med Genet. 1999 Dec 3;87(4):331–8.
Ahmad, A., et al. “Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate.Am J Med Genet, vol. 87, no. 4, Dec. 1999, pp. 331–38. Pubmed, doi:10.1002/(sici)1096-8628(19991203)87:4<331::aid-ajmg10>3.0.co;2-k.
Ahmad A, Kahler SG, Kishnani PS, Artigas-Lopez M, Pappu AS, Steiner R, Millington DS, Van Hove JL. Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. Am J Med Genet. 1999 Dec 3;87(4):331–338.

Published In

Am J Med Genet

DOI

ISSN

0148-7299

Publication Date

December 3, 1999

Volume

87

Issue

4

Start / End Page

331 / 338

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Pyruvate Carboxylase Deficiency Disease
  • Lactic Acid
  • Ketosis
  • Intellectual Disability
  • Infant
  • Humans
  • Follow-Up Studies
  • Female
  • Dose-Response Relationship, Drug