What is Lysinuric Protein Intolerance?

Lysinuric Protein Intolerance (LPI) is a rare autosomal recessive disorder caused by a defect in the LAT-1 protein in the epithelial cells of the small intestine and renal tubules. This leads to impaired transport of dibasic amino acids (lysine, arginine, and ornithine) across the plasma membrane, resulting in multi-organ involvement.

Which department should be consulted for Lysinuric Protein Intolerance?

English name: Lysinuric Protein Intolerance, LPI.

Aliases: Cationic aminoaciduria, Familial protein intolerance, 2-Hyperdibasic aminoaciduria.

Departments: Pediatrics, Neonatology, Gastroenterology.

What are the causes of Lysinuric Protein Intolerance?

Mutations in the SLC7A7 gene on chromosome 14q11.2 lead to structural and functional defects in the dibasic amino acid transporter. The pathogenesis varies depending on the transporter's expression site:

• In the digestive tract, impaired transporter function prevents lysine, arginine, and ornithine from entering the bloodstream, lowering their plasma concentrations.
• In the kidneys, defective reabsorption of these amino acids increases their urinary excretion.
• In the liver, impaired transport and reabsorption disrupt the urea cycle, causing hyperammonemia.

Who is commonly affected by Lysinuric Protein Intolerance?

Symptoms may appear during infancy. The estimated incidence ranges from 1 in 60,000 to 1.7 in 100,000 worldwide.

What are the clinical manifestations of Lysinuric Protein Intolerance?

Typical symptoms include recurrent vomiting, diarrhea, and protein-rich food aversion after weaning. The condition primarily affects the intestines, liver, and kidneys, with hyperammonemia as a key feature. Progressive multi-organ involvement may occur.

• Digestive system: Persistent vomiting, episodic diarrhea, protein aversion, hepatomegaly.
• Nervous system: Growth retardation, hypotonia; lethargy, ataxia, seizures, or coma after protein intake.
• Lungs: Progressive interstitial lung disease, pulmonary alveolar proteinosis.
• Kidneys: Proximal renal tubular dysfunction, nephrocalcinosis, renal amyloidosis, or failure.
• Other: Osteoporosis, pathologic fractures, leukopenia, thrombocytopenia, recurrent pancreatitis, hepatic amyloidosis.

How is Lysinuric Protein Intolerance diagnosed?

1. Typical symptoms: Recurrent vomiting, diarrhea, and protein aversion after weaning.
2. Lab tests: Reduced plasma levels of cationic amino acids (lysine, arginine, ornithine), elevated ammonia; increased urinary excretion, especially lysine.
3. Imaging: Long-bone X-rays may show osteoporosis, fractures, or delayed bone age; chest CT may reveal interstitial lung disease or alveolar proteinosis.
4. Genetic testing: SLC7A7 gene mutation analysis.

How is Lysinuric Protein Intolerance treated?

• Reducing hyperammonemia risk: Low-protein diet and citrulline supplementation.
• Supporting growth: Controlled protein intake (adjusted based on ammonia levels) to meet developmental needs.
• Managing complications: Corticosteroids/immunosuppressants for interstitial pneumonia; vitamin D and calcium for low bone density.

What is the prognosis of Lysinuric Protein Intolerance?

Early diagnosis and treatment significantly improve outcomes and reduce mortality. Delayed or inadequate management may lead to growth retardation, respiratory failure, or multi-organ dysfunction, which can be life-threatening.

How to prevent Lysinuric Protein Intolerance?

• Lifelong low-protein diet, with adjusted intake during growth (monitoring ammonia levels).
• Avoid trauma to prevent fractures.
• Preconception genetic counseling and prenatal diagnosis.