INTRAVENOUS L-CARNITINE AND ACETYL-L-CARNITINE IN MEDIUM-CHAIN ACYL-COENZYME-A DEHYDROGENASE-DEFICIENCY AND ISOVALERIC ACIDEMIA

The purpose of this study was to determine whether treatment with L-ca rnitine or acetyl-L-carnitine enhances the turnover of lipid or branch ed-chain amino acid oxidation in patients with inborn errors of metabo lism. Increasing i.v. doses Of L-carnitine and acetyl-L-carnitine were given to one patient with medium-chain acyl-CoA dehydrogenase deficie ncy and to another with isovaleric acidemia. Both patients were in sta ble condition and receiving Oral L-carnitine supplements. The excretio n of carnitine and disease-specific metabolites was measured. The inco rporation Of L-carnitine in the intracellular pool was demonstrated us ing stable isotopes and mass spectrometry. Increasing doses of either i.V. L-carnitine or acetyl-L-carnitine did not stimulate the excretion of octanoylcarnitine in the patient with medium-chain acyl-CoA dehydr ogenase deficiency, nor did it raise the plasma levels of either cis-4 -decenoate or octanoylcarnitine. Similarly, increasing doses of either i.v. L-carnitine or acetyl-L-carnitine did not enhance the excretion of isovalerylcarnitine in a patient with isovaleric acidemia. The excr etion of isovalerylglycine actually decreased. We conclude that there was no evidence of enhanced fatty acid beta-oxidation or enhanced bran ched-chain amino acid oxidation in vivo by the administration of high doses Of L-carnitine or acetyl-L-carnitine in these two patients. Beca use only one individual with each disorder was studied, the data are o nly indicative and may not necessarily be representative of all indivi duals with these disorders. Definite settlement of this issue will req uire further studies in additional subjects.