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.
Synopsis
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)
Laboratory
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)
Etiology
germline mutations in the amino acid transporter gene SLC7A7 (MIM.603593)
References
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
