ISOVALERIC ACIDEMIA - RESPONSE TO A LEUCINE LOAD AFTER 3 WEEKS OF SUPPLEMENTATION WITH GLYCINE, L-CARNITINE, AND COMBINED GLYCINE-CARNITINETHERAPY

Objective: To assess the effectiveness of glycine and carnitine therap y on isovaleryl conjugate excretion in isovaleric acidemia (IVA). Stud y design: Urinary isovalerylglycine (IVG) and isovalerylcarnitine (IVC ) were measured from 12-hour urine specimens collected overnight from an 8-year-old patient with IVA (who had no residual activity of isoval eryl-CoA dehydrogenase in fibroblasts) before and during 3-week course s of supplementation with glycine alone (250 mg/kg per day), L-carniti ne alone (100 mg/kg per day) therapy, and both of these agents combine d, with a 2 gm leucine challenge performed at the end of each treatmen t period. Results: Isovalerylglycine was the predominant metabolite ex creted throughout the study, and its mean value doubled with glycine t reatment. Isovalerylcarnitine excretion was minimal without carnitine supplementation. L-Carnitine therapy was associated with a 50% decline in excretion of IVG without a fully compensatory increase in IVC. The readdition of glycine to the carnitine regimen resulted in an increas e in IVG excretion. Leucine challenge resulted in a 2.7- and 2.4-fold increase of IVG and IVC excretion, respectively, during L-carnitine th erapy but not during glycine supplementation, and a 3.5- and 4-fold in crease in excretion of both metabolites during glycine plus L-carnitin e therapy. Total conjugate excretion was highest after a leucine load during combined glycine and L-carnitine therapy. Conclusions: Combined glycine and L-carnitine therapy maximally increases isovaleryl conjug ate excretion during metabolic stress but not under stable conditions.