Effect of treatment with glycine and L-carnitine in medium-chain acyl-coenzyme A dehydrogenase deficiency

To assess the relative contribution of glycine and carnitine conjugation pathways to total acyl-group excretion, we investigated the excretion of C6 to C10 dicarboxylic acids, C6 to C8 acylglycines, and C6 to C8 acylcarnitines in five symptom-free patients with medium-chain acyl-coenzyme A dehydrogenase deficiency during sequential 1-week periods as follows: (1) no treatment, (2) oral supplementation with glycine, 250 mg/kg per day, (3) oral supplementation with L-carnitine, 100 mg/kg per day, and (4) oral supplementation with both combined. In untreated patients, acylglycines and acylcarnitines represented 60% and less than 1% of the total metabolite excretion, respectively; the average acylglycine/acylcarnitine ratio was 70:1. Oral supplementation with glycine did not alter the excretion of acylglycines or acylcarnitines. L-Carnitine supplementation increased the acylcarnitine excretion sixfold and caused a 60% reduction in acylglycine excretion (p < 0.001); however, even with carnitine supplementation, acylglycine excretion was still 10 times greater than that of acylcarnitines. The results suggest that glycine conjugation was the major pathway for the disposal of C6 to C8 acyl moieties and that oral L-carnitine supplements may inhibit glycine conjugation. The findings cast doubt on the value of long-term treatment of medium-chain acyl-coenzyme A dehydrogenase deficiency with L-carnitine.