An atypical French form of pyruvate carboxylase deficiency

A further case of pyruvate carboxylase deficiency, French type, with a particular clinical presentation and evolution is described. The initial neonatal symptoms started with respiratory distress, severe metabolic acidosis and a tendency to hypoglycemia. However, the clinical course was not rapidly deteriorating. At the age of 6 months he presented acute neurological symptoms, respiratory difficulty, lactic acidosis and hyperammonemia. Amino and organic acid abnormalities strongly suggested pyruvate carboxylase deficiency, which was confirmed by enzymatic studies in cultured fibroblasts and liver necropsy. Progressive deterioration and bronchopneumonia with cardiac failure and renal insufficiency led to death. Anatomic-pathologic studies revealed periventricular cysts and diffuse hypomyelination. Prenatal diagnosis of a further sibling was performed. The neonatal clinical presentation, biochemical abnormalities, and the presence of periventricular cysts suggested a French phenotype. However, the clinical course was less severe, suggesting a residual enzymatic activity and a possible milder mutation.