National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Lysinuric protein intolerance


Other Names:
LPI; Dibasicamino aciduria II
Categories:
Lysinuric protein intolerance (LPI) is a genetic condition that is caused by the body's inability to digest the amino acids lysine, arginine, and ornithine. These are some of the building blocks of protein. Because the body cannot effectively break down these amino acids, which are found in many protein-rich foods, individuals experience nausea and vomiting after ingesting protein. Symptoms usually develop after infants are weaned and begin to eat solid foods. Without treatment, other signs and symptoms associated with protein intolerance may also occur, including short stature, muscle weakness, impaired immune function, and weak brittle bones (osteoporosis). The most serious symptoms involve the lung, kidney and heart. A lung disorder called pulmonary alveolar proteinosis may develop in some individuals, as can end-stage renal disease, coma and intellectual disability.

Lysinuric protein intolerance is caused by mutations in the SLC7A7 gene and is inherited in an autosomal recessive manner.  It is diagnosed based on the symptoms, laboratory and genetic testing. This condition is treated with a modified diet and medications. The long-term outlook depends on the age that LPI is diagnosed and the response to treatment.[1][2][3]
Last updated: 3/18/2019
The symptoms of lysinuric protein intolerance (LPI) may be different from individual to individual. Some people may be more severely affected than others and not everyone with LPI will have exactly the same symptoms.

Symptoms typically begin after an infant has stopped breastfeeding and started eating solid food.  These symptoms include:[1][3]

• Nausea and vomiting after a protein-rich meal
• Episodes of extreme tiredness (lethargy) and coma
• Growth delay resulting in short stature
• Muscle weakness
• Decreased immune function
• Weak, brittle bones (osteoporosis)
• Lung and kidney involvement
Last updated: 3/18/2019

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 83 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
30%-79% of people have these symptoms
Abnormal bleeding
Bleeding tendency
0001892
Abnormal circulating serine concentration 0012278
Alveolar proteinosis 0006517
Anemia
Low number of red blood cells or hemoglobin
0001903
Argininuria
High urine arginine levels
0003268
Bone marrow hypercellularity 0031020
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment
[ more ] 		0100543
Decreased glomerular filtration rate 0012213
Decreased HDL cholesterol concentration
Decreased circulating high-density lipoprotein cholesterol
Decreased HDL cholesterol
Low HDL-cholesterol
[ more ] 		0003233
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development
[ more ] 		0002750
Diarrhea
Watery stool
0002014
Elevated hepatic transaminase
High liver enzymes
0002910
Elevated plasma citrulline 0011966
Feeding difficulties
Feeding problems
Poor feeding
[ more ] 		0011968
Hemophagocytosis 0012156
Hepatic failure
Liver failure
0001399
Hepatomegaly
Enlarged liver
0002240
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Hyperalaninemia
Increased blood alanine
Increased serum alanine
[ more ] 		0003348
Hyperammonemia
High blood ammonia levels
0001987
Hypercholesterolemia
Elevated serum cholesterol
Elevated total cholesterol
Increased total cholesterol
[ more ] 		0003124
Hyperglutaminemia
High plasma glutamine
0003217
Hyperglycinemia
Elevated blood glycine levels
0002154
Hyperlysinuria
High urine lysine levels
0003297
Hyperprolinemia 0008358
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides
[ more ] 		0002155
Increased lactate dehydrogenase level 0025435
Increased LDL cholesterol concentration
Increased circulating LDL level
Increased LDL cholesterol
[ more ] 		0003141
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Leukopenia
Decreased blood leukocyte number
Low white blood cell count
[ more ] 		0001882
Oral aversion 0012523
Osteopenia 0000938
Osteoporosis 0000939
Proteinuria
High urine protein levels
Protein in urine
[ more ] 		0000093
Respiratory insufficiency
Respiratory impairment
0002093
Steatorrhea
Fat in feces
0002570
Thrombocytopenia
Low platelet count
0001873
Vomiting
Throwing up
0002013
5%-29% of people have these symptoms
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect
[ more ] 		0001627
Coma 0001259
Hepatic amyloidosis 0012280
Hypofibrinogenemia 0011900
Increased serum ferritin
Elevated serum ferritin
High ferritin level
Increased ferritin
Increased serum ferritin level
[ more ] 		0003281
Increased serum zinc 0011424
Lethargy 0001254
Membranous nephropathy 0012578
Ornithinuria 0003532
Oroticaciduria
High urine orotic acid levels
0003218
Pancreatitis
Pancreatic inflammation
0001733
Psychotic episodes 0000725
Renal amyloidosis 0001917
Renal fibrosis 0030760
Tubulointerstitial nephritis 0001970
1%-4% of people have these symptoms
Antinuclear antibody positivity 0003493
Complement deficiency 0004431
Decreased circulating antibody level 0004313
Growth hormone deficiency 0000824
Increased circulating antibody level 0010702
Pathologic fracture
Spontaneous fracture
0002756
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections
[ more ] 		0002718
Percent of people who have these symptoms is not available through HPO
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine
[ more ] 		0003355
Autosomal recessive inheritance 0000007
Cutis laxa
Loose and inelastic skin
0000973
Fine hair
Fine hair shaft
Fine hair texture
Thin hair shaft
Thin hair texture
[ more ] 		0002213
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Hyperextensible skin
Hyperelastic skin
Skin hyperelasticity
Stretchable skin
[ more ] 		0000974
Increased serum lactate 0002151
Infantile onset
Onset in first year of life
Onset in infancy
[ more ] 		0003593
Malnutrition 0004395
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia
Low or weak muscle tone
0001252
Nausea 0002018
Pulmonary hemorrhage 0040223
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures
[ more ] 		0002757
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ] 		0003202
Sparse hair 0008070
Splenomegaly
Increased spleen size
0001744
Stage 5 chronic kidney disease 0003774
Truncal obesity 0001956
Showing of 83 |
Last updated: 7/1/2020
Lysinuric protein intolerance is caused by a genetic change in the SLC7A7 gene.[4] 
Last updated: 3/18/2019
Lysinuric protein intolerance is inherited in an autosomal recessive pattern.[4] All individuals inherit two copies of each gene. To have lysinuric protein intolerance, a person must have a mutation in both copies of the SLC7A7 gene in each cell. There is nothing either parent can do, before or during pregnancy, to cause a child to have this.

People with autosomal recessive conditions inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive disorder typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, each child has a:

• 25% (1 in 4) chance to have the disorder
• 50% (1 in 2) chance to be an unaffected carrier like each parent
• 25% (1 in 4) chance to be unaffected and not be a carrier

Last updated: 3/18/2019
The diagnosis of lysinuric protein intolerance is made when an individual is noted to have the specific symptoms of this condition.  It is confirmed by specific laboratory testing and genetic testing of the SLC7A7 gene.[3]
Last updated: 3/18/2019

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Lysinuric protein intolerance is treated through a protein-restricted diet. In addition, medications are used to help prevent the build-up of nitrogen and ammonia in the blood. Other treatments may be used depending on the specific symptoms that are present.[2]
Last updated: 3/18/2019
The long-term outlook for people with lysinuric protein intolerance may depend on how early the condition is diagnosed and how soon treatment is started.[2] 
Last updated: 3/18/2019
The exact number of people with lysinuric protein intolerance is unknown.  It has been reported in about 200 individuals worldwide.  One-third of those are of Finnish origin. The prevalence in Finland is thought to be about 1/60,000.[3]
Last updated: 3/18/2019

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Lysinuric protein intolerance. This website is maintained by the National Library of Medicine.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Lysinuric protein intolerance. Click on the link to view a sample search on this topic.

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  1. Lysinuric protein intolerance. Genetics Home Reference (GHR). March 2008; http://ghr.nlm.nih.gov/condition/lysinuric-protein-intolerance.
  2. Mauhin V, Habarou R, Gobin S, Servais A, Brassier A, Grisel C, Roda C et al. Update on Lysinuric Protein Intolerance, a multi-faceted disease retrospective cohort analysis from birth to adulthood. Orphanet Jl of Rare Dis. Jan 5, 2017; 12(1):https://www.ncbi.nlm.nih.gov/pubmed/28057010.
  3. Nunes V, Niinikoski H. Lysinuric protein intolerance. GeneReviews. Updated Apr 12, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1361/.
  4. Lysinuric protein intolerance; LPI. Online Mendelian Inheritance in Man (OMIM). Updated 9/18/2015; https://www.omim.org/entry/222700.