Rare Ophthalmology News

Disease Profile

Lysinuric protein intolerance

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

E72.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

LPI; Dibasicamino aciduria II

Categories

Congenital and Genetic Diseases; Metabolic disorders

Summary

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]

Symptoms

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

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.

Cause

Lysinuric protein intolerance is caused by a genetic change in the SLC7A7 gene.[4]

Diagnosis

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]

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.

    Treatment

    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]

    Organizations

    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

      Learn more

      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.

          References

          1. Lysinuric protein intolerance. Genetics Home Reference (GHR). March 2008; https://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.

          Rare Ophthalmology News

          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
          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
          Intraalveolar phospholipid accumulation
          0006517
          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