Metabolic studies of carnitine in a child with propionic acidemia

Carnitine metabolism was studied in a 7-y-old boy with propionic acidemia due to an almost total deficiency of propionyl-CoA carboxylase. The initial diagnosis was made at 3 wk of age followed by numerous episodes of metabolic acidosis despite a low-content branch-chain amino acid diet containing supplemental biotin. Although clinically stable and in a nonacidotic state, the plasma concentration of total carnitine was normal (38.9 microM; normal = 46 +/- 10, mean +/- SD, n = 30) whereas free carnitine was decreased (5.7 microM; normal = 37 +/- 8) and short-chain acylcarnitines were increased (28.6 microM; normal = 5.7 +/- 3.5). Skeletal muscle and liver specimens obtained at open biopsy had low total and free carnitine contents and increased ratio of short-chain acylcarnitines to free carnitine. Short-chain acylcarnitine content was low in liver but increased in skeletal muscle. The liver contained fatty vacuoles, enlarged mitochondria with paracrystalline inclusions, and numerous peroxisomes whereas the skeletal muscle also had lipid vacuoles and an increase in number and size of mitochondria. A carnitine challenge test (100 mg L-carnitine/kg body wt via a gastrostomy tube) resulted in a peak plasma carnitine concentration at 120 min. With maintenance therapy of 100 mg L-carnitine/kg/day the plasma free carnitine remained relatively low, the plasma glycine concentration decreased, and urinary acylcarnitine excretion increased. This study demonstrates that the alterations in carnitine and its derivatives observed in plasma and urine reflect the same type of altered distribution in tissue and provides further data on the effects of L-carnitine therapy.