Pyruvate Carboxylase Deficiency, Infantile Type

Infantile pyruvate carboxylase (PC) deficiency (Type A) is a rare, severe form of PC deficiency characterized by infantile-onset, mild to moderate lactic acidemia, and a generally severe course.

Epidemiology

The specific prevalence of type A pyruvate carboxylase deficiency is not known but it has been reported most often in Native Americans from North American Algonquian-speaking groups including the Mi'kmaq, Cree, and Ojibwa tribes. In these groups, the carrier frequency may be as high as 1/10.

Clinical description

Patients with Type A PC deficiency usually first present with symptoms at the age of two to five months, often after normal early development. Clinical manifestations include mild to moderate metabolic acidosis with acute vomiting and tachypnea, failure to thrive, apathy, delayed intellectual and motor development, hypotonia, pyramidal dysfunction, ataxia, nystagmus and seizures. Renal tubular acidosis has also been reported.

Etiology

PC deficiency is caused by mutations in the PC gene (11q13.4-q13.5).

Diagnostic methods

Biochemical testing shows hypoglycemia and ketosis, increased alanine and proline levels, but normal citrulline and lysine levels, along with a normal lactate-to-pyruvate ratio despite acidemia, and normal hydroxybutyrate/acetoacetate (H/A) ratio in plasma. Blood lactic acid levels are usually between 2 and 10 mmol/l. PC enzyme activity assay demonstrating deficiency of the PC enzyme in fibroblasts is also diagnostic, along with mutations in the PC gene identified via molecular genetic testing.

Genetic counseling

PC deficiency is inherited in an autosomal recessive manner.

Prognosis

Most affected patients die in infancy or in early childhood. Surviving children require special care and schooling.