RESUMEN
BACKGROUND: Patients with propionic acidemia usually present in the neonatal period with life-threatening ketoacidosis, often complicated by hyperammonemia. It was thought that the neurologic abnormalities seen in this disease were exclusively the consequences of these acute crises. Experience with 2 patients with propionic acidemia indicates that this disease may present first with prominent neurologic disease without the life-threatening episodes of ketoacidosis that usually serve as the alerting signals for a diagnosis of an organic acidemia. OBJECTIVE: To examine the clinical and metabolic aspects of 2 patients with a phenotype that suggested disease of the basal ganglia. DESIGN: Examination of patterns of organic acids of the urine and enzyme assay for propionyl-CoA carboxylase in fibroblasts and lymphocytes. SETTING: Referral population to a biochemical genetics laboratory. PATIENTS: Two patients whose prominent features were hypotonia followed by spastic quadriparesis and choreoathetosis. Both had seizures. One patient was mildly mentally retarded but grew normally physically. The other had profound mental retardation and failure to thrive; he also self-mutilated his lower lip. Self-injurious behavior has not been reported in this disease. MAIN OUTCOME MEASURES: Clinical description, blood ammonia levels, organic acid levels in the urine, and enzyme activity. RESULTS: Excretion of metabolites, including methylcitrate, was typical. Residual activity of propionyl-CoA carboxylase approximated 5% of the control in each patient. CONCLUSIONS: Propionic acidemia can present as a pure neurologic disease without acute episodes of massive ketoacidosis. Hyperammonemia may occur after infancy in some patients, presenting as Reye syndrome.