Medicine:Lysinuric protein intolerance

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Lysinuric protein intolerance
Other namesHyperdibasic aminoaciduria type 2,Cationic aminoaciduria or Familial protein intolerance

Lysinuric protein intolerance (LPI) is an autosomal recessive[1] metabolic disorder affecting amino acid transport.

About 140 patients have been reported, almost half of them of Finland origin. Individuals from Japan, Italy, Morocco and North Africa have also been reported plus one in Bixby, Oklahoma.

Signs and symptoms

Infants with LPI are usually symptom-free when breastfed because of the low protein concentration in human milk, but develop vomiting and diarrhea after weaning. The patients show failure to thrive, poor appetite, growth retardation, enlarged liver and spleen, prominent osteoporosis and osteopenia,[2] delayed bone age and spontaneous protein aversion. Forced feeding of protein may lead to convulsions and coma. Mental development is normal if prolonged episode of hyperammonemia can be avoided. Some patients develop severe pulmonary and kidney complications. High levels of plasma glutamine and glycine are observed.


It has been associated with SLC7A7.[3]


Lysinuric protein intolerance has an autosomal recessive pattern of inheritance.

In LPI, urinary excretion of cationic amino acids (ornithine, arginine and lysine) is increased and these amino acids are poorly absorbed from the intestine. Therefore, their plasma concentrations are low and their body pools become depleted. Deficiency of arginine and ornithine restricts the function of the urea cycle and leads to hyperammonemia after protein-rich meals. Deficiency of lysine may play a major role in the skeletal and immunological abnormalities observed in LPI patients.


The diagnosis is based on the biochemical findings (increased concentrations of lysine, arginine and ornithine in urine and low concentrations of these amino acids in plasma, elevation of urinary orotic acid excretion after protein-rich meals, and inappropriately high concentrations of serum ferritin and lactate dehydrogenase isoenzymes) and the screening of known mutations of the causative gene from a DNA sample.


Treatment of LPI consists of protein-restricted diet and supplementation with oral *GeneReview/NIH/UW entry on Lysinuric Protein Intolerance citrulline. Citrulline is a neutral amino acid that improves the function of the urea cycle and allows sufficient protein intake without hyperammonemia.


Under proper dietary control and supplementation, the majority of the LPI patients are able to have a nearly normal life. However, severe complications including pulmonary alveolar proteinosis and chronic kidney disease may develop even with proper treatment.[4]Fertility appears to be normal in women, but mothers with LPI have an increased risk for complications during pregnancy and delivery.[5]


  1. "Lysinuric protein intolerance" (Free full text). The American Journal of Medicine 59 (2): 229–240. August 1975. doi:10.1016/0002-9343(75)90358-7. PMID 1155480. 
  2. Online Mendelian Inheritance in Man (OMIM) 222700
  3. "SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance". Nat. Genet. 21 (3): 297–301. March 1999. doi:10.1038/6815. PMID 10080183. 
  4. "Nephropathy advancing to end-stage renal disease: a novel complication of lysinuric protein intolerance". J. Pediatr. 150 (6): 161–164. June 2007. doi:10.1016/j.jpeds.2007.01.043. PMID 17517249. 
  5. "Hazards associated with pregnancies and deliveries in lysinuric protein intolerance". Metabolism 55 (2): 224–231. February 2006. doi:10.1016/j.metabol.2005.08.016. PMID 16423630. 

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