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