Pyruvate Carboxylase Deficiency

Abstract

Pyruvate carboxylase (PC) deficiency is a rare disorder with autosomal recessive inheritance. Generally, two clinical and biochemical phenotypes of isolated PC deficiency can be distinguished. The so-called French phenotype presents in the neonatal period with severe lactic acidemia and is clinically characterized by failure to thrive, anorexia, vomiting, weak cry, convulsions, stupor, hyporeactivity, hypotonia, tachypnea, dyspnea, respiratory failure, and subsequently hypertonia, extrapyramidal tract signs and severely retarded development. Most children die within the first few months of life. The North American phenotype is less severe. Patients become symptomatic between 2 and 5 months of age with developmental delay, failure to thrive, apathy, hypotonia, spasticity, ataxia, nystagmus and convulsions. Episodes of vomiting, tachypnea, tachycardia, ataxia and lactic acidosis occur, precipitated by metabolic or infectious stress. Some patients die in the infantile period, while most of the survivors are grossly retarded. A few exceptional patients have been reported who despite the episodic metabolic derangement have a normal or near normal motor and mental development. Formerly, Leigh syndrome was thought to represent another clinical phenotype of PC deficiency, but this could not be confirmed.