Lysinuric protein intolerance: a two-year trial of dietary supplementation therapy with citrulline and lysine.

In lysinuric protein intolerance, a disease resulting from an autosomal recessive disorder of diamino acid transport, citrulline, unlike arginine and lysine, is absorbed normally from the intestine. In 19 patients with LPI, the status after 2 years of treatment with citrulline or citrulline + lysine was compared with that during the preceding period of treatment with arginine. Administration of citrulline led to improved protein nutrition, as indicated by increases in daily protein intake, blood hemoglobin values, and plasma albumin and valine concentrations. Normal excretion of orotic acid indicated adequate urea cycle function. Seven of the nine stunted children had marked catch-up growth. Of four patients biopsied twice and having initially severe fatty degeneration of the liver, two had improved histology. However, hepato- and splenomegaly, and several biochemical abnormalities in the serum remained unchanged. Giving additional lysine did not enhance the favorable effect, but in some patients provoked abdominal cramps and diarrhea. Citrulline is the most valuable agent for treatment of LPI. Although not curative, it corrects the deficiency of the urea cycle intermediates and protects the patients from hyperammonemia and its consequences.