title: Lysinuric protein intolerance (LPI): a multi organ disease by far more complex than a classic urea cycle disorder.
abstract: Lysinuric protein intolerance (LPI) is an inherited defect of cationic amino acid (lysine, arginine and ornithine) transport at the basolateral membrane of intestinal and renal tubular cells caused by mutations in SLC7A7 encoding the y(+)LAT1 protein. LPI has long been considered a relatively benign urea cycle disease, when appropriately treated with low-protein diet and l-citrulline supplementation. However, the severe clinical course of this disorder suggests that LPI should be regarded as a severe multisystem disease with uncertain outcome. Specifically, immune dysfunction potentially attributable to nitric oxide (NO) overproduction secondary to arginine intracellular trapping (due to defective efflux from the cell) might be a crucial pathophysiological route explaining many of LPI complications. The latter comprise severe lung disease with pulmonary alveolar proteinosis, renal disease, hemophagocytic lymphohistiocytosis with subsequent activation of macrophages, various auto-immune disorders and an incompletely characterized immune deficiency. These results have several therapeutic implications, among which lowering the l-citrulline dosage may be crucial, as excessive citrulline may worsen intracellular arginine accumulation.
authors.affiliation: APHP, Reference Center for Inherited Metabolic Disease, Hôpital Robert Debré, F-75019 Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Ogier de Baulny
authors.forename: Manuel
authors.initials: M
authors.lastname: Schiff
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
mesh_terms: D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000473:pathology; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000473:pathology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000473:pathology; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D055501:Macrophage Activation Syndrome / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000628:therapy; D056806:Urea Cycle Disorders, Inborn / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000628:therapy
chemical_list: D027283:Large Neutral Amino Acid-Transporter 1; D001120:Arginine; D008239:Lysine