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Lysinuric protein intolerance (LPI) is a very rare inherited multisystem condition caused by distrubance in amino acid metabolism. It is mainly found in Italy and Finland where prevalence is 1/60,000. The metabolic disturbance in LPI causes increased renal excretion and reduced absorption from intestine of cationic amino acids, and orotic aciduria. Patients affected by LPI may present with vomiting, diarrhea, failure to thrive, hepatosplenomegaly, bone marrow abnormalities, osteopenia, episodes of hyperammoniaemic coma, mental retardation, altered immune response, chronic renal disease, and lung involvement (mostly pulmonary alveolar proteinosis - PAP - and, to a lesser extent, interstitial lung disease). Pulmonary involvement represents a major cause of impaired clinical course and fatal outcome. LPI is inherited according to autosomal recessive modality. It is caused by defective cationic amino acid transport at the basolateral membrane of epithelial cells in the kidney and intestine. LPI is caused by mutations of solute carrier family 7A member 7 (SLC7A7) located at chromosome 14q11.2. Diagnosis requires amino acid assays in plasma and urine where increased urinary excretion and low plasma concentration of lysine, arginine, and ornithine indicate positive diagnosis. Treatment revolves around protein-restricted diet and supplement of lysine, ornithine, and citrulline. The complication of pulmonary alveolar proteinosis has been reported to be successfully treated by whole lung lavage. Prognosis varies depending on pulmonary complications. |