Effect of carnitine administration on glycine metabolism in patients with isovaleric acidemia: Significance of acetylcarnitine determination to estimate the proper carnitine dose

In isovaleric acidemia (IVA), accumulated isovaleryl-CoA in the mitochondrion induces variable metabolic disturbances. To remove intramitochondrial isovaleryl groups, glycine therapy has been advocated primarily. On the other hand, secondary carnitine deficiency has been documented in this disorder and carnitine supplementation alone has been reported to be effective. In the present study, we administered carnitine and glycine to patients with IVA and investigated serum carnitine and urinary excretion of total and free carnitine, acylcarnitine profile (i.e., isovalerylcarnitine and acetylcarnitine), and isovalerylglycine. By adding carnitine to glycine supplementation, more isovalerylglycine, not only isovalerylcarnitine, was excreted in the urine. Acetylcarnitine was detected in the urine only when sufficient carnitine was supplemented. We concluded that combined therapy of glycine and carnitine is more effective and safer to eliminate isovaleryl-CoA in IVA than conventional therapy using either glycine or carnitine. Urinary acetylcarnitine concentration might be a good marker indicating the optimal dose of L-carnitine supplementation.