tyrosinaemia type I

Last edited 11/2021 and last reviewed 12/2021

Tyrosinaemia type I is the result of deficiency of fumarylacetoacetates hydrolase.

Tyrosinemia type I (hepatorenal tyrosinemia, HT-1)

• is an autosomal recessive condition (OMIM 276700)
• is a rare metabolic disease caused by a defect in tyrosine catabolism
• is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome
• caused by an autosomal recessive inherited deficiency of the enzyme fumarylacetoacetate hydrolase (FAH), which is the last enzyme in the tyrosine catabolic pathway converting fumarylacetoacetate (FAA) into fumarate and acetoacetate
• clinical symptoms
  • typically begin before 2 years of age, with the majority of children presenting before the age of 6 months with evidence of acute liver failure and renal dysfunction
  • neurologic crises, manifesting as painful episodes affecting extremity and/or abdominal function, accompanied by hypertension and hyponatremia, may present at any time and may result in respiratory failure and death
  • a few affected children may present over the age of 2 years with isolated coagulopathy or other signs of liver dysfunction, renal tubular disease, hypophosphatemic rickets, and failure to thrive
  • all children with HT-1 are at high risk for hepatocellular carcinoma (HCC)
  • an effective medical treatment with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC, nitisinone) exists but requires early identification of affected children for optimal long-term results

Reference:

• Chinsky JM, Singh R, Ficicioglu C, et al. Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med. 2017;19(12):. doi:10.1038/gim.2017.101
• van Ginkel WG, Rodenburg IL, Harding CO, Hollak CEM, Heiner-Fokkema MR, van Spronsen FJ. Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1. Paediatr Drugs. 2019;21(6):413-426. doi:10.1007/s40272-019-00364-4