Pyruvate Carboxylase Deficiency: A Benign Variant with Normal Development

ABSTRACT: The devastating nature of a pyruvate carboxylase deficiency is underscored by the uniformly fatal outcome of the neonatal (French) type and the severely disabling and ultimately fatal outcome of the infantile (North American) type. We report a ?-y-old girl with metabolic and biochemical features of the North American phenotype. Remarkably, the clinical course has been benign with preservations of motor and mental abilities. The residual enzyme activity in cultured skin fibroblast homogenates was 1.8% and cross-reacting material was present in normal abundance and electrophoretic mobility. She has had several episodes of metabolic acidosis with elevated lactate, pyruvate, alanine, ß-hydroxybutyrate, acetoacetate, lysine, and proline values, and undetectably low aspartate concentrations. These crises have been managed by rehydration and bicarbonate therapy. We are unable to provide a satisfactory explanation for the uniquely benign clinical course that has been experienced by this patient.