Lysinuric
protein intolerance (LPI) typically presents after an infant is weaned
from breast milk or formula; variable findings include recurrent
vomiting and episodes of diarrhea, episodes of stupor and coma after a
protein-rich meal, poor feeding, aversion to protein-rich food, failure
to thrive, hepatosplenomegaly, and muscular hypotonia. Over time,
findings include: poor growth, osteoporosis, involvement of the lungs
(progressive interstitial changes, pulmonary alveolar proteinosis) and
of the kidneys (progressive glomerular and proximal tubular disease),
hematologic abnormalities (normochromic or hypochromic anemia,
leukopenia, thrombocytopenia, erythroblastophagocytosis in the bone
marrow aspirate), and a clinical presentation resembling the
hemophagocytic lymphohistiocytosis/macrophagic activation syndrome.
Hypercholesterolemia, hypertriglyceridemia, and acute pancreatitis can
also be seen.

The
diagnosis is established in an individual with clinical and laboratory
features suggestive of LPI including elevated 24-hour urinary excretion
of cationic amino acids, especially lysine. Identification of biallelic SLC7A7 pathogenic variants confirms the diagnosis.

Treatment of manifestations:
In acute hyperammonemic crises: intravenous administration of arginine
chloride and nitrogen-scavenger drugs (sodium benzoate, sodium
phenylacetate) to block ammonia production; reduction of excess nitrogen
in the diet; provision of energy as carbohydrates to reduce catabolism.
Long-term: dietary protein restriction; oral supplementation with
citrulline and nitrogen-scavenger drugs, L-lysine-HCl, and carnitine;
whole-lung lavage to improve respiratory function in persons with
pulmonary alveolar proteinosis.