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lysinuric protein intolerance

MIM.222700 14q11.2

Wednesday 25 January 2006

Lysinuric protein intolerance (LPI) (MIM.222700) is an inherited autosomal recessive hyperdibasic aminoaciduria.

LPI is a very rare disease which was first described in 1965 in two infant Finnish siblings. The majority of cases reported in the literature concern patients from Finland, where the disease prevalence is about 1 in 60,000.

It is caused by defective cationic amino acid (CAA) (L-arginine, L-lysine, L-ornithine) transport, normally exerted by the y+L system, at the basolateral membrane of epithelial cells in the intestine and kidney.

Clinical findings in LPI patients include: vomiting, diarrhea, failure to thrive, hepatosplenomegaly, bone marrow abnormalities, osteoporosis, episodes of coma, mental retardation, altered immune response, chronic renal disease and lung involvement, mainly PAP.

LPI is caused by mutations of the solute carrier family 7A member 7 (SLC7A7) gene. The SLC7A7 (MIM.603593) gene encodes the y+LAT-1 protein which is the light chain subunit of a member of the heterodimeric amino acid transporters (HATs) family.


- pulmonary anomalies

  • acute respiratory insufficiency
  • pulmonary hemorrhages
  • pulmonary alveolar proteinosis

- cholesterol granulomas
- renal insufficiency
- immune complex-mediated glomerulonephritis
- hepatic insufficiency
- fatty degeneration
- cirrhosis
- anemia
- thrombocytopenia
- osteoporosis
- protein malnutrition
- protein intolerance
- failure to thrive
- retarded physical development
- diarrhea
- malabsorption
- hepatomegaly (enlarged liver)
- vomiting
- liver cirrhosis
- mental retardation
- attacks of stupor and asterixis
- skeletal fragility
- osteopenia
- intermittent macrophagic activation syndrome (hemophagocytic lymphohistiocytosis)
- micronodular cirrhosis of the liver (8163273)
- extensive fatty change in hepatocytes (8163273)
- pulmonary alveolar proteinosis
- glomerulonephritis with predominant IgA deposition (8163273)


- lysinuria
- ornithinuria
- argininuria
- hyperammonemia
- low blood urea
- leukopenia
- chronic hyperammonemia while cationic aminoaciduria (lysine, arginine and ornithine) during L-citrulline supplementation
- bone marrow examination: red cell and granulocytes phagocytosis by histiocytes and granulocytes precursors (8949349)


- germline mutations in the amino acid transporter gene SLC7A7 (MIM.603593)


- Ceruti M, Rodi G, Stella GM, Adami A, Bolongaro A, Baritussio A, Pozzi E, Luisetti M. Successful whole lung lavage in pulmonary alveolar proteinosis secondary to lysinuric protein intolerance: a case report. Orphanet J Rare Dis. 2007 Mar 26;2:14. PMID: 17386098

- Parto K, Kallajoki M, Aho H, Simell O. Pulmonary alveolar proteinosis and glomerulonephritis in lysinuric protein intolerance: case reports and autopsy findings of four pediatric patients. Hum Pathol. 1994 Apr;25(4):400-7. PMID: 8163273

- Necropsy findings in lysinuric protein intolerance. McManus DT, Moore R, Hill CM, Rodgers C, Carson DJ, Love AH. J Clin Pathol. 1996 Apr;49(4):345-7. PMID: 8655715