Reduced nitric oxide production by L-arginine deficiency in lysinuric protein intolerance exacerbates intravascular coagulation

Lysinuric protein intolerance (LPI) results in low serum L-arginine, hypera mmonemia, mental retardation, thrombocytopenia, and an increased frequency of bowel movements. Our objective was to evaluate the effects of low serum L-arginine, the essential substrate for reactions catalyzed by nitric oxide synthetase (NOS), on the serum nitric oxide (NO) level and coagulation act ivity in a patient with LPI. A 37-year-old Japanese man who presented with abdominal pain and subnormal fasting levels of serum L-arginine and L-lysin e was found to have LPI. The result of oral administration of diamino acids was an increased in urine and a decrease in serum, thus confirming the dia gnosis. A decrease in the platelet count and an increase in the plasma leve ls of thrombin-antithrombin III complex (TAT) and fibrin degradation produc ts (FDPs) indicated the presence of subclinical intravascular coagulation. Serum levels of NO derivatives and I-arginine were determined after intrave nous administration of L-arginine. The effects of intravenous L-arginine or transdermal nitroglycerin on the plasma level of TAT were also investigate d. Serum levels of NO derivatives were significantly reduced in the LPI pat ient versus the healthy control group (n = 5). Intravenous administration o f L-arginine increased the serum level of NO derivatives and the platelet c ount and reduced plasma TAT and FDP levels. The plasma level of TAT was als o reduced by transdermal nitroglycerin. A decrease in the serum level of L- arginine in patients with LPI appears to result in a decrease in NO product ion. The improvement in plasma TAT levels produced by administration of int ravenous L-arginine or transdermal nitroglycerin suggests that intravascula r coagulation is exacerbated by the decrease of NO production in patients w ith LPI. Copyright (C) 1999 by W.B. Saunders Company.