Genetics of Pyruvate Carboxylase Deficiency Treatment & Management

Updated: Mar 15, 2019
  • Author: Richard E Frye, MD, PhD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Treatment

Medical Care

Treatments in patients with pyruvate carboxylase deficiency (PCD) are aimed at stimulating the pyruvate dehydrogenase complex (PDC) and providing alternative fuels. Correction of the biochemical abnormality can reverse some symptoms, but central nervous system damage progresses regardless of treatment.

The PDC can provide an alternative pathway for pyruvate metabolism PDC activity can be optimized by cofactor supplementation with thiamine and lipoic acid and administration of dichloroacetate. Increased pyruvate metabolism through this pathway can help reduce the pyruvate and lactate levels.

Biotin supplementation is given to help optimize the residual enzyme activity but is usually of little use.

Citrate supplementation reduces the acidosis and provides the needed substrate in the citric acid cycle.

Aspartic acid supplementation allows the urea cycle to proceed and reduces the ammonia level.

One patient reportedly was successfully treated with a continuous nocturnal gastric drip feeding of uncooked cornstarch.

Triheptanoin has reportedly reversed hepatic failure and biochemical abnormalities in one case by presumably providing a source of acetyl-CoA and anaplerotic propionyl-CoA. However, life expectancy was not prolonged.

Orthotopic liver transplantation has reversed the biochemical abnormalities in one patient. [8]

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Consultations

Evaluation by an expert in metabolic and genetic disorders is necessary to confirm the diagnosis, guide the appropriate treatment, and determine the prognosis.

Genetic counseling for the parents is important in order to determine the risk of recurrence in future pregnancies.

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Diet

Diet has a small effect on outcome.

A high-carbohydrate, high-protein diet may help to maintain an anabolic state and prevent activation of gluconeogenesis.

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