Lysinuric protein intolerance ( LPI ): treatment with citrulline and lysine

Abstract

LPI is an autosomal recessive defect of diamino acid transport in renal tubular and intestinal epithelium, and hepatocytes. This leads to deficiency of ornithine and other urea cycle intermediates, and inadequate function of the cycle which results in hyperammonemia after protein intake, and protein aversion. Lysine shortage may contribute to the growth failure of the patients. Our patients have earlier been treated with an arginine supplement. We have now shown that, while the intestinal absorption is very poor for arginine, it is intact for citrulline, another urea cycle intermediate. Since autumn 1976 our patients have been given 1.5 g/kg of dietary protein daily supplemented with 2-3 g citrulline and 1-2 g lysine. The protein aversion decreased in 13/21 patients, growth accelerated in 12/21, and urinary orotic acid excretion rate normalized in 9/11 as a sign of improved nitrogen tolerance. 4 patients had very fragile and sparse hair; this normalized during the therapy. Gastrointestinal complaints appeared during the treatment in 6/21; these disappeared when lysine supplementation was stopped. Hepato- and splenomegalia, increased plasma lactate dehydrogenase, leukocytopenia and trombocytopenia, and fasting plasma and urinary amino acids remained unchanged. They may depend on lysine deficiency. The severe intestinal transport defect of lysine seems to invalidate the oral route for lysine supplementation. We suggest that citrulline, possibly with lysine, should replace arginine in the treatment of LPI.