Defective metabolic clearance of plasma arginine and ornithine in lysinuric protein intolerance

Abstract

Fasting plasma lysine, arginine, and ornithine concentration is clearly statistically decreased in patients with lysinuric protein intolerance (LPI). In seven LPI patients and five reference subjects, one suffering from classic cystinuria, arginine and ornithine were infused intravenously at a stepwise-increased rate. Plasma steady-state concentration of the infused diamino acid was larger in LPI patients than in the reference subjects, although the patients lost more into the urine. The increase in plasma ornithine and urea concentration on arginine infusion was similar in both groups. Calculated metabolic clearance rates (MCR) of arginine and ornithine were clearly smaller in LPI patients than in the reference subjects. Infusion of lysine brought about a clear decrease in the MCR of arginine; this was similar in both groups of subjects. These findings suggest a defect in the transport of diamino acids into liver cells, such as has been earlier demonstrated in the renal tubuli. Such a general cellular transport defect of diamino acids would explain both basic characteristics of LPI: renal loss of diamino acids and slow urea synthesis.