Disease Directory Tyrosinemia Type 1
Metabolic

Tyrosinemia Type 1

Also known as: HT1, fumarylacetoacetase deficiency, FAH deficiency, hepatorenal tyrosinemia

Prevalence

1-9 per 100,000 (Orphanet)

Onset

Infantile, Childhood

Type

Autosomal recessive genetic

Gene

FAH

About Tyrosinemia Type 1

Tyrosinemia type 1 is the most severe form of tyrosinemia, caused by deficiency of fumarylacetoacetase (FAH), the final enzyme in the tyrosine degradation pathway. Accumulation of toxic metabolites, particularly succinylacetone, causes progressive liver failure, renal tubular dysfunction (Fanconi syndrome), and a high risk of hepatocellular carcinoma. Nitisinone (NTBC/Orfadin), which blocks an upstream step in the pathway, has dramatically improved outcomes and is now standard of care.

Common Clinical Features

Liver failure Hepatocellular carcinoma risk Renal Fanconi syndrome Rickets Porphyria-like crises Elevated alpha-fetoprotein Failure to thrive

Clinical Trial Eligibility Tips

What to know before applying to Tyrosinemia Type 1 trials.

Nitisinone (NTBC) treatment is near-universal — trials may study dose optimization, gene therapy, or nitisinone alternatives

Alpha-fetoprotein (AFP) level is a critical biomarker and tumor surveillance marker required at baseline

Succinylacetone in urine or blood is the diagnostic gold standard and an eligibility confirmation marker

Liver transplantation cures the hepatic phenotype — transplanted patients are typically ineligible for hepatic gene therapy trials

Patient Resources

Patient Organization

Tyrosinemia Network

Visit website ↗

Orphanet

European reference resource for rare diseases (ORPHA:882)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

Search NORD ↗

Find recruiting Tyrosinemia Type 1 trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Tyrosinemia Type 1. Updated daily.

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