Tyrosinaemia type I (and II)

Alternative names
  • Hepatorenal tyrosinaemia
  • Fumarylacetoacetate hydrolase (FAH) deficiency
About the condition Tyrosinaemia type I is an amino acid disorder. It is a hereditary disease that if left untreated may cause liver failure or cirrhosis, kidney damage and rickets. Liver cancer may eventually develop.
Inheritance Autosomal recessive
Year screening started in WA 2005
Incidence in Australia Approximately 1 in 100,000 births
Enzyme defect Fumarylacetoacetate hydrolase deficiency
Symptoms if untreated The most severe form of the disease usually causes problems within the first months of life, such as poor weight gain, vomiting, enlarged liver and spleen, and bleeding. If left untreated the disease progresses to liver failure with jaundice, coagulopathy, cirrhosis and ascites. Other symptoms of the condition include:
  • Hepatomas
  • Renal Fanconi syndrome
  • Rickets
  • ‘Cabbage-like’ odour
  • Peripheral neuropathy, seizures
Metabolites on bloodspot screening
  • Increased tyrosine
  • Increased succinylacetone (second-tier test)
Diagnostic tests
  • Plasma amino acids
  • Urine amino and organic acids
  • Renal and liver function tests
  • FAH gene analysis
Treatment
  • Phenylalanine and tyrosine restricted diet
  • NTBC (inhibitor of 4-hydroxyphenylpyruvate dioxygenase) and liver transplant if indicated
Screening issues
  • There is considerable variability in the level of tyrosine in the blood in Tyrosinaemia type I. Some infants will therefore not be reliably detected by the current screening test
  • Tyrosinaemia type II is a rare disorder of tyrosine metabolism that causes corneal ulceration and painful thickened skin of the hands and feet. It may additionally be detected with this screening strategy