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Screening & Prevention >> Newborn Screening >> Amino Acid Disorders >> Tyrosinemia type 1

Tyrosinemia type 1

Disorder Category

an amino acid (urea cycle) disorder

Screening

Finding

elevated tyrosine

Tested By

tandem mass spectrometry (MS/MS); sensitivity~80%*; specificity=99.98% [Schulze: 2003]

Names

Tyrosinemia type 1

Hereditary tyrosinemia type 1 (HT1)

Hereditary infantile tyrosinemia

Hepatorenal tyrosinemia

Fumarylacetoacetase deficiency

Fumarylacetoacetate hydrolase deficiency (FAH deficiency)

ICD-9

270.2, Disturbance of aromatic amino-acid metabolism

Overview

Due to a deficiency of fumarylacetoacetase (FAH), patients may have the inability to break down tyrosine and remove succinylacetone from the blood resulting in liver and kidney, failure to thrive and rickets.

Prevalence

about 1/125,000 live births [Schulze: 2003]

Inheritance

autosomal recessive

Prenatal Testing

DNA testing, succinylacetone testing, or enzyme analysis by amniocentesis or CVS.

Clinical Characteristics

With treatment, >90% survival rate can be expected, along with normal growth, normalization of liver function and prevention of cirrhosis, correction of renal tubular acidosis and resolution of secondary rickets. Treatment may not affect the incidence of hepatic cancer. Treatment consists of a diet low in tyrosine and phenylalanine and use of a drug (nitisone or NTBC) that prevent formation of succinylacetone, the toxic agent responsible for liver and kidney damage. Patients with evidence of cirrhosis or liver cancer require liver transplantation. If treatment is begun too late, rickets, failure to thrive, and hypotonia may result. Without treatment, chronic problems ensue, including: liver disease leading to cirrhosis and hepatocellular carcinoma, renal tubular disease (Fanconi syndrome), seizures, cardiomyopathy, and coagulation disorders. Repeated neurologic crises may occur involving mental status change, peripheral neuropathy, and/or respiratory failure. Death usually occurs by 10 years of age.

Initial symptoms may include:
  • severe liver involvement in the young infant with:
    • jaundice,
    • ascites,
    • loss of clotting factor synthesis,
    • GI bleeding;
  • or development later in the first year of:
    • liver dysfunction;
    • renal involvement;
    • growth failure;
    • rickets; and
    • "boiled cabbage" or "rotten mushroom" odor to the body and urine.

Follow-up on positive screening test

Quantitative plasma amino acid analysis, urine organic acid analysis.

Primary care management

Upon notification of the + screen

If the diagnosis is confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Tyrosinemia type 1 info for parents, STAR-G);
  • Support initiation and maintenance of dietary restriction of phenylalanine and tyrosine;
  • Treatment with Nitisinone [NTBC or 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione)], a competitive inhibitor of an upstream enzyme that reduces the production of toxic metabolites;
  • Vitamin D supplements may be indicated for affected children;
  • Regular blood and urine tests to monitor amino acid, succinylacetone, and alpha-fetoprotein levels; kidney and liver function; and diet may be indicated;
  • CT or MRI liver scans for early diagnosis of scarring or cancer may be indicated;
  • Liver transplation may be considered to prevent hepatocellular carcinoma;
  • For those identified after irreversible sequelae, assist in management of liver and kidney disease and support with developmental and educational interventions.

Specialty Care Management

Initial consultation and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management. Ongoing collaboration with gastroenterology and nephrology.

Resources

Links

For Professionals

Tyrosinemia type 1 info for professionals, STAR-G
On the Screening, Technology and Research in Genetics (STAR-G) site, one of a series of Disorder Fact Sheets for Professionals; structured list of information about the condition, with links to more information.

ACT Sheet for Tyrosinemia type 1 from ACMG (pdf 128kb)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.

ACMG ACT Sheets and Confirmatory Algorithms
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.

Tyrosinemia type 1, Emergency Protocol
A protocol for management of the patient with a positive screen for tyrosinemia type 1, from the New England Consortium of Metabolic Programs.

Tyrosinemia type 1, GeneTests.org
Excellent review by Lisa Sniderman, Cristine Trahms, and C. Ronald Scott, including clinical description, differential, management, genetic counseling, molecular genetics, and a bibliography.

Utah Newborn Screening Program
The site provides information and statistics about the program and related legislation, training for practices, and the conditions screened for.

For Parents

Tyrosinemia type 1 info for parents, STAR-G
From the Screening, Technology and Research in Genetics (STAR-G) site, providing information for parents about tyrosinemia type 1 and links to other sites including parent support groups.

Tyrosinemia type 1, Genetics Home Reference
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference site.

National Urea Cycle Disorders Foundation
The National Urea Cycle Disorders Foundation, a non-profit organization, provides support services and information for families; medical lectures on urea cycle disorders; nutrition and medication resources; and information about events and conferences.

Services

Newborn Screening Programs

Utah Newborn Screening Program, more info...
44 Mario Capecchi Drive
Salt Lake City, UT84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening

Pediatric Genetics

Metabolic Clinic, more info...
100 Mario Capecchi Drive
Salt Lake City, UT84113
Phone: 801-585-2457
Fax: 585-7252
http://www.ped.med.utah.edu/divisions/divisions.htm

See all Pediatric Genetics services providers (3) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for articles on tyrosinemia type 1 in the last 5 years.

Authors

Reviewing Author: Nicola Longo MD, PhD, 3/2007
Compiled and edited by: Alfred Romeo RN, PhD, 3/2007
Content Last Updated: 3/2008

Page Bibliography

Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.
Pediatrics. 2003;111(6 Pt 1):1399-406. PubMed abstract
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