Combined Hyperlipidemia in Patients with Lysinuric Protein Intolerance

Background And Aims: Lysinuric protein intolerance (LPI) is an autosomal recessive disorder characterized by defective transport of cationic amino acids lysine, arginine, and ornithine. Low plasma concentrations of arginine and ornithine lead to impaired urea cycle function and, subsequently, decreased protein tolerance. Patients often develop natural aversion to protein-rich foods, which may predispose them to nutritional problems. The objective of this retrospective study was to investigate lipid values and efficacy of lipid-lowering therapy in patients with LPI.

Methods And Results: Serum total and high-density-lipoprotein (HDL)-cholesterol and triglyceride concentrations were analyzed in 39 Finnish LPI patients (14 males) aged 3-64 years. Dietary intakes were analyzed from food records. Mean [standard deviation (SD)] serum and HDL-cholesterol and triglyceride concentrations were 7.16 (2.13) mmol/l, 1.21 (0.58) mmol/l, and 4.0 (2.4) mmol/l, respectively. Patients with renal dysfunction had marginally higher total cholesterol and significantly higher triglyceride concentration than patients without renal impairment. Twenty-two patients were started on 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (atorvastatin or simvastatin). After 6 months, serum cholesterol and triglyceride concentrations had decreased by 32% (p < 0.001), whereas HDL-cholesterol had increased by 13% (p = 0.016).

Conclusion: Serum cholesterol and triglyceride values are markedly elevated in LPI patients. Although the mechanism of combined hyperlipidemia remains unknown and is not explained by fat consumption, hyperlipidemia is clearly progressive with age, suggesting that starting statin therapy early is probably beneficial. Statins are well-tolerated and efficacious in LPI.