Overview of symptoms and treatment for lysinuric protein intolerance

Lysinuric protein intolerance (LPI) is caused by dysfunction of the dibasic amino acid membrane transport owing to the functional abnormality of y⁺L amino acid transporter-1 (y⁺ LAT-1). LPI is associated with autosomal recessive inheritance and pathological variants in the responsible gene SLC7A7 are also observed. The pathophysiology of this disease had earlier been understood as a transport defect in polarized cells (e.g., intestinal or renal tubular epithelium); however, in recent years, transport defects in non-polarized cells such as lymphocytes and macrophages have also been recognized as important. Although the former can cause death, malnutrition, and urea cycle dysfunction (hyperammonemia), the latter can induce renal, pulmonary, and immune disorders. Furthermore, although therapeutic interventions can prevent hyperammonemic episodes to some extent, progression of pulmonary and renal complications cannot be prevented, thereby influencing prognosis. Such pathological conditions are currently being explored and further investigation would prove beneficial. In this study, we have summarized the basic pathology as revealed in recent years, along with the clinical aspects and genetic features.