Carnitine deficiency and L-carnitine supplementation in lysinuric protein intolerance.

The aim of the study was to investigate the prevalence and mechanisms of development of carnitine deficiency in patients with lysinuric protein intolerance (LPI). In our cohort of 37 Finnish patients with LPI, 8 (8-52 years of age) have been diagnosed with hypocarnitinemia. Their free and total serum carnitine levels, acyl carnitine profiles, renal function, diet, and medication were compared with the data from 8 age- and sex-matched patients with LPI not treated with carnitine supplementation. In patients with LPI, hypocarnitinemia was strongly associated with female sex, renal insufficiency, and the use of ammonia-scavenging drugs. Of the 8 hypocarnitinemic patients, 3 complained of muscle weakness, and their symptoms disappeared during carnitine supplementation. Oral lysine supplementation did not correct hypocarnitinemia in our patients. The patients with LPI are at considerable risk for carnitine deficiency. Supplementation of hypocarnitinemic LPI patients with oral L-carnitine improved serum total carnitine values, but the ratio of free and total carnitine remained subnormal in all supplemented patients except one. Furthermore, decreased ratio of free and total serum carnitine was common even in LPI patients with normal total serum carnitine concentration.

Oral supplementation corrects plasma lysine concentrations in lysinuric protein intolerance.

In lysinuric protein intolerance (LPI), intestinal absorption and renal tubular reabsorption of arginine, ornithine, and lysine are impaired due to a defective cationic amino acid transporter. Deficiency of arginine and ornithine restricts the function of the urea cycle, leading to hyperammonemia after protein load, and to strong protein aversion. Mealtime supplements of citrulline, another urea cycle intermediate that uses other transport mechanisms, prevent postprandial hyperammonemia and improve protein tolerance. Deficiency of lysine, an essential amino acid, most probably also contributes to the symptoms of LPI. We investigated possibilities to improve the availability of lysine for tissues by increasing plasma lysine concentration. Six patients with LPI were started on short-term oral lysine supplementation that was administered with their regular citrulline doses and standard low-protein meals. L-Lysine in consecutive doses of 0.55 and 1.1 mmol/kg caused profuse diarrhea in first 3 patients. To avoid gastrointestinal side effects, the 3 other patients were started on smaller lysine supplements of only 0.05 mmol/kg per dose, given 3 times daily for 3 days. All pre- and postprandial plasma lysine concentrations remained within normal range in 2 of the 3 patients studied. Even after the larger doses, no significant effects on the urea cycle were seen. We conclude that low-dose oral lysine supplementation normalizes plasma lysine concentration in patients with LPI, and is safe and well tolerated at least in short-term use.