Effect of lysine infusion on urea cycle in lysinuric protein intolerance

Poor intestinal absorption and excessive renal loss of dibasic amino acids result in low plasma concentrations in patients with lysinuric protein into lerance (LPI). Arginine and ornithine deficiency impair the function of the urea cycle and cause hyperammonemia after protein intake, while chronic ly sine deficiency may cause growth failure and lead to reduced bone density i n such patients. Since high lysine concentrations inhibit several enzymes o f the urea cycle in the liver, lysine supplementation may induce hyperammon emia in LPI. We thus studied how LPI patients tolerate high plasma lysine b y intravenous (IV) infusion of 3.3 mmol/kg lysine hydrochloride over 90 min utes in 6 adult patients and 4 healthy controls. The plasma lysine concentr ation (mean +/- SD, range) peaked in the patients (9,114 +/- 1,864, 7,156 t o 12,044 mu mol/L) and controls (10,185 +/- 2,253, 7,714 to 13,122 mu mol/L ) at 90 minutes. Urinary lysine excretion peaked in the second 2-hour urine collection in the patients (4,582 +/- 1,276, 3,018 to 6,315 mu mol/m(2) bo dy surface area per hour) and in the first 2-hour collection in the control s (5,373 +/- 1,766, 3,551 to 7,286 mu mol/m(2)/h). Two patients had mild na usea but no hyperammonemia and one patient had moderate hyperammonemia (pea k, 112 mu mol/L) at the end of the infusion. Orotic acid excretion increase d in 2 subjects with a peak excretion rate of 33 and 251 mu mol/m(2)/h in t he third 2-hour collection after starting the load. All other subjects rema ined asymptomatic and showed no change in plasma ammonia or urinary orotic acid excretion. We thus conclude that an acute increase in plasma lysine ca used minimal clinical or biochemical untoward effects in patients with LPI. Moderate increases in plasma lysine after low-dose oral supplementation wi th lysine or well-absorbed lysine derivatives are probably well tolerated i n LPI. Copyright (C) 2000 by W.B. Saunders Company.