Tyrosinemia type 1

Title

Other Names:

Tyrosinemia type I; Hepatorenal tyrosinemia; Fumarylacetoacetase deficiency; Tyrosinemia type I; Hepatorenal tyrosinemia; Fumarylacetoacetase deficiency; FAH deficiency See More

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Kidney and Urinary Diseases; Congenital and Genetic Diseases; Digestive Diseases; Kidney and Urinary Diseases; Metabolic disorders; Nervous System Diseases; Newborn Screening; Rare Cancers See More

Summary 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]

Last updated: 12/21/2017

Symptoms 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.

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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	Abnormal blood clotting	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
Glomerulosclerosis		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 islet-cell hyperplasia		0004510
Paralytic ileus		0002590
Periodic paralysis		0003768
Renal Fanconi syndrome		0001994
Renal insufficiency	Renal failure Renal failure in adulthood [ more ]	0000083

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 6/1/2019

Do you have updated information on this disease? We want to hear from you.

Diagnosis 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 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.

Last updated: 12/21/2017

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: 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

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential metabolic diagnoses include classic galactosemia, hereditary fructose intolerance, and fructose 1,6 diphosphatase deficiency, Wilson's disease and some mitochondrial disorders (see these terms). Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Tyrosinemia type 1. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Tyrosinemia type 1. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for Tyrosinemia type 1:
NBS Connect

Learn More 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.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My son is 18 days old and has been diagnosed with tyrosinemia type 1. Is there any hope of curing my son's illness? See answer

Have a question? Contact a GARD Information Specialist.

References References

Tyrosinemia. Genetics Home Reference (GHR). August 2015; https://ghr.nlm.nih.gov/condition/tyrosinemia.
Tyrosinemia: Information for Physicians and Other Health Care Providers. Illinois Department of Public Health Web site. http://www.idph.state.il.us/HealthWellness/fs/tyrosinemia.htm. Accessed 4/26/2010.
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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