Pyruvate Carboxylase Deficiency, Benign Type

Benign pyruvate carboxylase (PC) deficiency (Type C) is a rare, very mild form of PC deficiency characterized by episodic metabolic acidosis and normal or mildly delayed neurological development.

Epidemiology

Benign PC deficiency is a very rare form of PC deficiency and has been described in fewer than 10 patients to date. No ethnic predilection has been reported.

Clinical description

Onset typically occurs during the first year of life with episodic metabolic acidosis associated with lactic acidemia and occasionally with ketoacidosis during metabolic stress. Neurological development is normal or mildly impaired. Other signs include dystonia, episodic ataxia, dysarthria, transitory hemiparesis and seizures.

Etiology

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

Diagnostic methods

Blood lactic acid levels are usually between 2 and 5 mmol/l. The abnormal biochemical parameters found in severe forms of PC deficiency are absent in patients with Type C, although lysine, proline and alanine may be elevated, while citrulline is normal. 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

Pyruvate carboxylase deficiency is inherited in an autosomal recessive manner.