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Vascular endothelial dysfunction resulting from L-arginine deficiency in a patient with lysinuric protein intolerance.

ABSTRACT: Although L-arginine is the only substrate for nitric oxide (NO) production, no studies have yet been reported on the effect of an L-arginine deficiency on vascular function in humans. Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of dibasic amino acid transport caused by mutations in the SLC7A7 gene, resulting in an L-arginine deficiency. Vascular endothelial function was examined in an LPI patient who was shown to be a compound heterozygote for two mutations in the gene (5.3-kbp Alu-mediated deletion, IVS3+1G-->A). The lumen diameter of the brachial artery was measured in this patient and in healthy controls at rest, during reactive hyperemia (endothelium-dependent vasodilation [EDV]), and after sublingual nitroglycerin administration (endothelium-independent vasodilation [EIV]) using ultrasonography. Both EDV and NO(x) concentrations were markedly reduced in the patient compared with those for the controls. They became normal after an L-arginine infusion. EIV was not significantly different between the patient and controls. Positron emission tomography of the heart and a treadmill test revealed ischemic changes in the patient, which were improved by the L-arginine infusion. Thus, in the LPI patient, L-arginine deficiency caused vascular endothelial dysfunction via a decrease in NO production.

SUBMITTER: Kamada Y

PROVIDER: S-EPMC209374 | biostudies-literature | 2001 Sep

REPOSITORIES: biostudies-literature

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Vascular endothelial dysfunction resulting from L-arginine deficiency in a patient with lysinuric protein intolerance.

Kamada Y Y Nagaretani H H Tamura S S Ohama T T Maruyama T T Hiraoka H H Yamashita S S Yamada A A Kiso S S Inui Y Y Ito N N Kayanoki Y Y Kawata S S Matsuzawa Y Y

The Journal of clinical investigation 20010901 5

Although L-arginine is the only substrate for nitric oxide (NO) production, no studies have yet been reported on the effect of an L-arginine deficiency on vascular function in humans. Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of dibasic amino acid transport caused by mutations in the SLC7A7 gene, resulting in an L-arginine deficiency. Vascular endothelial function was examined in an LPI patient who was shown to be a compound heterozygote for two mutations in the ge ...[more]

PMID: 11544277

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Project description:BACKGROUND:Lysinuric protein intolerance (LPI; MIM# 222700) is a rare metabolic disorder caused by a defective cationic amino acids (CAA) membrane transport leading to decreased circulating plasma CAA levels and resulting in dysfunction of the urea cycle. Short stature is commonly observed in children with LPI and has been associated with protein malnutrition. A correlation between LPI and growth hormone deficiency (GHD) has also been postulated because of the known interaction between the AA arginine, ornithine, and lysine and growth hormone (GH) secretion. Our report describes a case of GHD in an LPI patient, who has not presented a significant increase in growth velocity with recombinant-human GH (rhGH) therapy, suggesting some possible pathogenic mechanisms of growth failure. CASE PRESENTATION:The proband was a 6-year-old boy, diagnosed as suffering from LPI, erythrophagocytosis (HP) in bone marrow, and short stature. Two GH provocative tests revealed GHD. The patient started rhGH therapy and a controlled-protein diet initially with supplementation of oral arginine and then of citrulline. At 3-year follow-up, no significant increase in growth velocity and in insulin-like growth factor-1 (IGF-1) levels was observed. Inadequate nutrition and low plasmatic levels of arginine, ornithine, lysine, and HP may have contributed to his poor growth. CONCLUSION:Our case suggests that growth failure in patients with GHD and LPI treated with rhGH could have a complex and multifactorial pathogenesis. Persistently low plasmatic levels of lysine, arginine, and ornithine, associated with dietary protein and caloric restriction and systemic inflammation, could determine a defect in coupling GH to IGF-1 production explaining why GH replacement therapy is not able to significantly improve growth impairment. We hypothesize that a better understanding of growth failure pathophysiology in these patients could lead to the development of more rational strategies to treat short stature in patients with LPI.

Dataset Information

Vascular endothelial dysfunction resulting from L-arginine deficiency in a patient with lysinuric protein intolerance.

Publications

Vascular endothelial dysfunction resulting from L-arginine deficiency in a patient with lysinuric protein intolerance.

Similar Datasets

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