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Metabolic Disorder

Tyrosinemia Type I

HIGH SEVERITY

A severe autosomal recessive disorder of amino acid metabolism caused by deficiency of fumarylacetoacetate hydrolase (FAH). Leads to accumulation of toxic metabolites causing liver failure, kidney dysfunction, and neurologic crises. Untreated, fatal in childhood. Newborn screening allows early treatment.

Global Affected

80.0K

Countries

19

Symptoms

Hepatomegaly
Liver failure
Renal Fanconi syndrome
Rickets
Neurologic crises (pain, paralysis)
Failure to thrive
Hypoglycemia
Hepatocellular carcinoma risk

Treatment Options

NTBC (nitisinone)
Dietary restriction of tyrosine and phenylalanine
Specialized metabolic formula
Liver transplant (for acute failure or HCC)
Management of renal Fanconi syndrome
Treatment of rickets
Supportive care for neurologic crises

Risk Factors

1FAH gene mutations
2Autosomal recessive inheritance
3Family history of tyrosinemia
4Consanguineous parents
5Certain populations (Scandinavia, Quebec)

Diagnostic Methods

  • 1Elevated succinylacetone in blood or urine
  • 2Elevated tyrosine and alpha-fetoprotein
  • 3FAH enzyme assay or genetic testing
  • 4Liver biopsy (if needed)
  • 5Newborn screening (succinylacetone)
  • 6Prenatal diagnosis available

Prognosis

Without treatment: Death by age 2 from liver failure or HCC. With NTBC and diet: 90%+ survival; liver and kidney function preserved; neurologic crises prevented; HCC risk reduced but still requires surveillance. Quality of life good with treatment. Lifelong treatment required. Early diagnosis through newborn screening is critical for optimal outcomes.

Prevention

  • Newborn screening
  • Genetic counseling
  • Carrier screening in high-risk populations
  • Prenatal diagnosis
  • Preimplantation genetic diagnosis
  • Early initiation of NTBC

Research Status

NTBC (nitisinone) is a life-saving treatment that blocks toxic metabolite formation. Combined with dietary restriction of tyrosine and phenylalanine. Liver transplant reserved for acute liver failure or malignancy. Newborn screening has transformed outcomes.

Sources

  • https://www.ncbi.nlm.nih.gov/books/NBK1514
  • https://www.mayoclinic.org/diseases-conditions/tyrosinemia
  • https://rarediseases.org/rare-diseases/tyrosinemia-type-i

Medical Disclaimer

This information is for educational purposes only. Always consult healthcare professionals for medical advice, diagnosis, and treatment.