Pyruvate carboxylase deficiency


Pyruvate carboxylase deficiency (PCD) is a rare non-sex linked (autosomal) disorder that results from an insufficient amount of the enzyme pyruvate carboxylase. This disorder is inherited as a recessive trait and it is known to be caused by more than one different mutation in the same gene (allelic variants).


Type A, or infantile onset, PCD may be fatal prior to birth, or it may not present any symptoms until approximately three months of age. These individuals will show severe physical and mental delay. Additionally, children affected with type A PCD have a progressive degeneration of the entire brain and nervous system (necrotizing encephalomyelopathy) that eventually leads to death.


PCD is diagnosed primarily through blood tests to determine the blood concentrations of lactate and pyruvate. Extremely high levels of both of these chemicals in the blood indicate that a congenital problem in cellular metabolism is most likely present. PCD is often differentiated from other cellular metabolic disorders by the extreme speed with which glucose levels in the blood drop during fasting (fasting hypoglycemia) and the abnormally low levels of the chemical aspartic acid in the blood. PCD can be tested prenatally by measuring the activity of pyruvate carboxylase in chorionic villi samples.


Without prenatal administration of enzyme replacement therapy (which is currently not available), in which the developing fetus is given an artificial form of pyruvate carboxylase, individuals affected with either type A or type B PCD will die either prior to birth or, generally, within the first six months of life. Without prenatal enzyme replacement therapy, most children affected with PCD are born with such brain and nervous system dysfunction that a decision has to be made about treatment to sustain life.


Administration of aspartic acid has been successful in decreasing the pyruvate and lactate concentrations in the blood of some PCD affected individuals. But, this treatment does not repair the damage to the pyruvate carboxylase enzyme, so progressive degeneration of the nervous system is slowed only slightly and the outcome is still death. Biotin (a B-complex vitamin) is a coenzyme to pyruvate carboxylase. It has been shown that type B PCD is responsive to treatment with biotin while type A is not. Therefore, in the rare instance of a liveborn child with type B PCD, life may be extended through the administration of biotin.