Lysinuric protein intolerance

Lysinuric protein intolerance (LPI), also known as hyperdibasic aminoaciduria type 2 or familial protein intolerance, is a rare inherited metabolic disorder caused by defective transport of the dibasic amino acids lysine, arginine, and ornithine in the intestinal and renal tubular epithelial cells. It is caused by biallelic pathogenic variants in the SLC7A7 gene, which encodes the y+L amino acid transporter 1 (y+LAT1). The impaired absorption and increased renal loss of these amino acids leads to their deficiency in the body, which in turn disrupts the urea cycle and causes hyperammonemia after protein-rich meals. Symptoms typically appear after weaning, when dietary protein intake increases. Affected infants and children commonly develop vomiting, diarrhea, and failure to thrive. Many patients develop a natural aversion to protein-rich foods. Hyperammonemia episodes can cause lethargy, confusion, and in severe cases, coma. Over time, LPI can affect multiple organ systems. Hepatosplenomegaly is common, and patients are at risk for progressive interstitial lung disease (pulmonary alveolar proteinosis), renal disease, osteoporosis, and hematologic abnormalities including anemia, leukopenia, and thrombocytopenia. An increased susceptibility to infections and a predisposition to hemophagocytic lymphohistiocytosis (HLH) have also been reported. Some patients develop immune dysregulation and autoimmune features. Treatment is primarily dietary, involving protein restriction to prevent hyperammonemia while ensuring adequate caloric intake through carbohydrates and fats. Oral supplementation with citrulline, a neutral amino acid that bypasses the defective transporter and can replenish the urea cycle intermediates, is a cornerstone of management. Nitrogen-scavenging agents such as sodium benzoate or sodium phenylbutyrate may be used during acute hyperammonemic crises. Lysine and carnitine supplementation may also be considered. Despite treatment, long-term complications such as pulmonary alveolar proteinosis and renal disease remain significant challenges, and regular multidisciplinary follow-up is essential.

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