About Lysinuric Protein Intolerance And Its Genetic Causes

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What Is Lysinuric Protein Intolerance?

Lysinuric protein intolerance (LPI) is a genetically inherited condition in which certain amino acids (namely ornithine, lysine, and arginine) are not adequately broken down in affected individuals. Due to their inability to break down these amino acids, these individuals are prone to experiencing nausea and vomiting soon after they eat protein-rich foods.

Even more problematic are the other symptoms that are frequently seen in those who are inflicted with LPI. These symptoms stem directly from the inability to digest protein and include:

  • Shortness in height
  • Brittle and weak bones that can easily fracture (osteoporosis)
  • Immune system problems
  • Enlarged organs, particularly the spleen and liver

Another severely problematic symptom of LPI is pulmonary alveolar proteinosis. Pulmonary alveolar proteinosis is a condition in which excess protein concentrates in the lungs. Due to this excess build up, normal functions of the lungs are affected. In some cases, pulmonary alveolar proteinosis is life-threatening.

Excess protein also can build up in the kidneys of LPI sufferers and this often leads to a serious condition that is referred to as end-stage renal disease. In this condition, the kidneys become blocked and cannot adequately do one their most important jobs, which is to remove fluid and waste materials from the body.

Yet another harmful condition that can arise in individuals having LPI is an excess build up of ammonia in the blood. In the worst cases, this excess ammonia leads to severe cognitive problems and even coma.

Although it does not discriminate against any particular group, LPI is more common in the Japanese and Finnish populations than in other populations. Symptoms generally arise shortly after birth and, specifically, after affected infants begin eating solid foods that are rich in protein.

What Is Known About The Genetics Of Lysinuric Protein Intolerance?

Molecular geneticists have determined that LPI is inherited in an autosomal recessive fashion and is due to mutations in a gene that is referred to as SLC7A7. The SLC7A7 gene encodes a protein known as y+L amino acid transporter 1, or, in it shorthand form, simply y+LAT-1. This protein essentially serves as a shuttling service, as it is its job to transport ornithine, lysine, and arginine amino acid molecules from cell-to-cell throughout the body.

Mutations in the SLC7A7 gene cause either no or defective y+LAT-1 protein to be made, which means that there is no protein that is able to shuttle ornithine, lysine, and arginine amino acid molecules throughout the bodies of LPI sufferers. Specifically, the failure to move these amino acids is problematic because they are essential to many important processes. As one example, ornithine and arginine are important to a process known as the urea cycle. Deficiencies in the urea cycle causes the body to retain too much ammonia, as breaking down ammonia is one of the important functions of the urea cycle. In another example, lysine plays a key role in bone formation. Therefore, LPI sufferers often exhibit the bone defects, such as the ones that are described above (osteoporosis and shortness in height).

Unfortunately, there in no single treatment for LPI and therefore symptoms that can be treated need to be done so individually. This means that overall treatment usually is carried out by multi-specialist medical team, as many of the symptoms are very complex to treat and therefore require specific expertise. If you have a family history of Lysinuric Protein Intolerance and you are concerned that you may be at risk of passing this condition onto your children, it is recommended that you consult a genetic counselor.


Genetics Home Reference, National Institutes of Health, Lysinuric Protein Intolerance: https://ghr.nlm.nih.gov/condition/lysinuric-protein-intolerance

G. Sebastio and S. Fecarotta, Lysinuric Protein Intolerance, Gene Reviews, University of Washington: https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=lpi

S. Bröer, Lysinuric protein intolerance: one gene, many problems, Am. J. Physiol. Cell Physiol., 293:C450-C451 (2007). https://ajpcell.physiology.org/cgi/content/full/293/2/C540