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.