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, problems affecting the nervous system, and an increased risk of liver cancer. This condition is inherited in an autosomal recessive manner.^[1]

Last updated: 4/26/2010

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Aminoaciduria	90%
Abnormality of bone mineral density	7.5%
Abnormality of the spleen	7.5%
Hepatomegaly	7.5%
Abnormal bleeding	-
Abnormality of the abdominal wall	-
Acute hepatic failure	-
Ascites	-
Autosomal recessive inheritance	-
Cirrhosis	-
Elevated alpha-fetoprotein	-
Elevated hepatic transaminases	-
Elevated urinary delta-aminolevulinic acid	-
Enlarged kidneys	-
Episodic peripheral neuropathy	-
Failure to thrive	-
Gastrointestinal hemorrhage	-
Glomerulosclerosis	-
Hepatocellular carcinoma	-
Hypermethioninemia	-
Hypertrophic cardiomyopathy	-
Hypertyrosinemia	-
Hypoglycemia	-
Hypophosphatemic rickets	-
Nephrocalcinosis	-
Pancreatic islet-cell hyperplasia	-
Paralytic ileus	-
Periodic paralysis	-
Renal Fanconi syndrome	-
Renal insufficiency	-
Splenomegaly	-

Last updated: 9/1/2016

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. Early diagnosis and prompt treatment are essential for an improved prognosis. Some individuals require a liver transplant if their liver disease is already advanced before treatment begins.^[2]

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

Last updated: 4/26/2010

Management Guidelines

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 NORD Physician Guide for Tyrosinemia type 1 was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors. The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition.

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

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 studying or have studied Tyrosinemia type 1. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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.

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

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.

News & Events News & Events

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

References References

Tyrosinemia. Genetics Home Reference (GHR). 2008; http://ghr.nlm.nih.gov/condition=tyrosinemia. Accessed 2/3/2010.
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.

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