A patient with severe
pyruvate carboxylase deficiency presented at age 11 weeks with metabolic decompensation after routine immunization. She was
comatose, had severe lactic acidemia (22 mM) and
ketosis, low
aspartate and
glutamate, elevated
citrulline and
proline, and mild
hyperammonemia. Head magnetic resonance imaging showed
subdural hematomas and mild generalized brain
atrophy.
Biotin-unresponsive
pyruvate carboxylase deficiency was diagnosed. To provide
oxaloacetate, she was treated with high-dose
citrate (7.5 mol/kg(-1)/day(-1)),
aspartate (10 mmol/kg(-1)/day(-1)), and continuous drip feeding.
Lactate and
ketones diminished dramatically, and plasma
amino acids normalized, except for
arginine, which required supplementation. In the cerebrospinal fluid (CSF),
glutamine remained low and
lysine elevated, showing the treatment had not normalized brain chemistry. Metabolic decompensations, triggered by
infections or fasting, diminished after the first year. They were characterized by severe lactic and
ketoacidosis,
hypernatremia, and a tendency to
hypoglycemia. At age 3(1/2) years she has profound
mental retardation, spasticity, and grand mal and
myoclonic seizures only partially controlled by
anticonvulsants. The new treatment regimen has helped maintain metabolic control, but the neurological outcome is still poor.