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 mitoch ondrion induces variable metabolic disturbances. To remove intramitoch ondrial isovaleryl groups, glycine therapy has been advocated primaril y. On the other hand, secondary carnitine deficiency has been document ed in this disorder and carnitine supplementation alone has been repor ted to be effective. In the present study, we administered carnitine a nd glycine to patients with TVA, and investigated serum carnitine and urinary excretion of total and free carnitine, acylcarnitine profile ( i.e., isovalerylcarnitine and acetylcarnitine), and isovalerplglycine. By adding carnitine to glycine supplementation, more isovalerylglycin e, not only isovalerylcarnitine, was excreted in the urine. Acetylcarn itine was detected in the urine only when sufficient carnitine was sup plemented. We concluded that combined therapy of glycine and carnitine is more effective and safer to eliminate isovaleryl-CoA in IVA than c onventional therapy using either glycine or carnitine. Urinary acetylc arnitine concentration might be a good marker indicating the optimal d ose of L-carnitine supplementation.