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Disease Profile

Tyrosinemia type 1

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

All ages

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ICD-10

E70.2

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)

Tyrosinemia type I; Hepatorenal tyrosinemia; Fumarylacetoacetase deficiency;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Kidney and Urinary Diseases;

Summary

Tyrosinemia type 1 is a genetic disorder characterized by elevated blood levels of the amino acid tyrosine, a building block of most proteins. This condition is caused by a shortage of the enzyme fumarylacetoacetate hydrolase, one of the enzymes required for the multi-step process that breaks down tyrosine. This enzyme shortage is caused by mutations in the FAH gene. Symptoms usually appear in the first few months of life and include failure to thrive, diarrhea, vomiting, jaundice, cabbage-like odor, and increased tendency to bleed (particularly nosebleeds). Tyrosinemia type I can lead to liver and kidney failure, softening and weakening of the bones, problems affecting the nervous system, and an increased risk of liver cancer. This condition is inherited in an autosomal recessive manner.[1] Treatment should be started as soon as the condition is diagnosed and includes a diet restricted in tyrosine and phenylalanine along with nitisinone, a medication that blocks the second step in the tyrosine degradation pathway.[2][3]

Symptoms

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.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Generalized aminoaciduria
0002909
5%-29% of people have these symptoms
Acute hepatic failure
Acute liver failure
0006554
Hepatocellular carcinoma
0001402
Hepatomegaly
Enlarged liver
0002240
Rickets of the lower limbs
0006463
Splenomegaly
Increased spleen size
0001744
Percent of people who have these symptoms is not available through HPO
Abnormal bleeding
Bleeding tendency
0001892
Abnormality of coagulation
0001928
Abnormality of the abdominal wall
0004298
Ascites
Accumulation of fluid in the abdomen
0001541
Autosomal recessive inheritance
0000007
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Elevated alpha-fetoprotein
0006254
Elevated hepatic transaminase
High liver enzymes
0002910
Elevated urinary delta-aminolevulinic acid
0003163
Enlarged kidney
Large kidneys
0000105
Episodic peripheral neuropathy
0006949
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Glomerular sclerosis
0000096
Hypermethioninemia
Increased methionine in blood
0003235
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Hypertyrosinemia
Increased tyrosine in blood
0003231
Hypoglycemia
Low blood sugar
0001943
Hypophosphatemic rickets
0004912
Nephrocalcinosis
Too much calcium deposited in kidneys
0000121
Pancreatic isletcell hyperplasia
0004510
Paralytic ileus
0002590
Periodic paralysis
0003768
Renal Fanconi syndrome
0001994
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
  • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

    Treatment

    There is currently no cure for tyrosinemia type 1. Individuals with this condition need to be on a special diet restricted in two amino acids, tyrosine and phenylalanine, throughout life. Affected individuals may also be treated with a medication called nitisinone. Treatment should start as soon as the condition is diagnosed. Some individuals require a liver transplant if their liver disease is already advanced before treatment begins.[2][3]

    Detailed information on the treatment of tyrosinemia type 1 is available from GeneReviews.

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    • Nitisinone(Brand name: Generic version) Manufactured by Novitium Pharma
      FDA-approved indication: August 2019, the first generic capsule form of nitisinone was approved for the treatment of hereditary tyrosinemia type 1 (HT) in combination with dietary restriction of tyrosine and phenylalanine.
      National Library of Medicine Drug Information Portal
    • Nitisinone(Brand name: Nityr) Manufactured by Cycle Pharmaceuticals Ltd
      FDA-approved indication: July 2017, approved for the treatment of hereditary tyrosinemia type 1 (HT) in combination with dietary restriction of tyrosine and phenylalanine.
      National Library of Medicine Drug Information Portal
    • Nitisinone(Brand name: Orfadin®) Manufactured by Swedish Orphan AB
      FDA-approved indication: Adjunctive therapy to dietary restriction of tyrosine and phenylalanine in the treatment of hereditary tyrosinemia type 1. Available in capsule from since Januaray 2009. Available in oral suspension since April 2016.
      National Library of Medicine Drug Information Portal

    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 Tyrosinemia type 1. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
      • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

        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.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
        • 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 Tyrosinemia type 1. Click on the link to view a sample search on this topic.

          References

          1. Tyrosinemia. Genetics Home Reference (GHR). August 2015; https://ghr.nlm.nih.gov/condition/tyrosinemia.
          2. Tyrosinemia: Information for Physicians and Other Health Care Providers. Illinois Department of Public Health Web site. https://www.idph.state.il.us/HealthWellness/fs/tyrosinemia.htm. Accessed 4/26/2010.
          3. Sniderman King L, Trahms C, Scott CR. Tyrosinemia Type I. GeneReviews. May 25, 2017; https://www.ncbi.nlm.nih.gov/books/NBK1515/.

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