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Pathway Description
Lysinuric Protein Intolerance (LPI)
Homo sapiens
Disease Pathway
Lysinuric protein intolerance (LPI), also called hyperdibasic aminoaciduria, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the kidney function pathway. It is caused by a mutation in the SLC7A7 gene which encodes the Y+L amino acid transporter 1 protein, which is involved in the uptake of amino acids, both with sodium for neutral amino acids, and without for dibasic amino acids. In this disorder, the amino acids lysin, arginine and ornithine, found in protein, cannot be broken down, which can cause problems in the systems that use these amino acids, such as the urea cycle. LPI is characterized by a shortage of lysine, arginine and ornithine within the body, causing elevated ammonia levels in the blood. Symptoms of the disorder include failure to thrive after weaning, nausea and vomiting following a meal containing large amounts of protein, as well as osteoporosis, and lung and kidney problems. Treatment with a protein restricted diet is effective, as well as prescription of medication to lower the levels of ammonia in the blood. It is estimated that the LPI affects 1 in 60,000 individuals in certain populations such as in Finland and Japan, and less frequently outside these populations.
References
Lysinuric Protein Intolerance (LPI) References
[Metagen: LYSINURIC PROTEIN INTOLERANCE (LPI)](http://metagene.de/program/d.prg?id_d=61)
[OMIM: 222700](http://omim.org/entry/222700})
[NIH](http://ghr.nlm.nih.gov/condition/lysinuric-protein-intolerance)
Palacin M, Bertran J, Chillaron J, Estevez R, Zorzano A: Lysinuric protein intolerance: mechanisms of pathophysiology. Mol Genet Metab. 2004 Apr;81 Suppl 1:S27-37. doi: 10.1016/j.ymgme.2003.11.015.
Pubmed: 15050971
Broer S: Lysinuric protein intolerance: one gene, many problems. Am J Physiol Cell Physiol. 2007 Aug;293(2):C540-1. doi: 10.1152/ajpcell.00166.2007. Epub 2007 May 2.
Pubmed: 17475666
Camargo SM, Bockenhauer D, Kleta R: Aminoacidurias: Clinical and molecular aspects. Kidney Int. 2008 Apr;73(8):918-25. doi: 10.1038/sj.ki.5002790. Epub 2008 Jan 16.
Pubmed: 18200002
Sperandeo MP, Andria G, Sebastio G: Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene. Hum Mutat. 2008 Jan;29(1):14-21. doi: 10.1002/humu.20589.
Pubmed: 17764084
Sperandeo MP, Annunziata P, Ammendola V, Fiorito V, Pepe A, Soldovieri MV, Taglialatela M, Andria G, Sebastio G: Lysinuric protein intolerance: identification and functional analysis of mutations of the SLC7A7 gene. Hum Mutat. 2005 Apr;25(4):410. doi: 10.1002/humu.9323.
Pubmed: 15776427
Kidney Function References
Mount DB: Thick ascending limb of the loop of Henle. Clin J Am Soc Nephrol. 2014 Nov 7;9(11):1974-86. doi: 10.2215/CJN.04480413. Epub 2014 Oct 15.
Pubmed: 25318757
Giebisch G: Renal potassium channels: function, regulation, and structure. Kidney Int. 2001 Aug;60(2):436-45. doi: 10.1046/j.1523-1755.2001.060002436.x.
Pubmed: 11473623
Subramanya AR, Ellison DH: Distal convoluted tubule. Clin J Am Soc Nephrol. 2014 Dec 5;9(12):2147-63. doi: 10.2215/CJN.05920613. Epub 2014 May 22.
Pubmed: 24855283
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