Classification and goals - TYR I

Hypertyrosinemia is observed in three inherited disorders of tyrosine metabolism.

Tyrosinemia Type I (HT1) results from a deficiency of fumarylacetoacetate hydrolase; an enzyme responsible for the breakdown of the aromatic amino acid tyrosine.
Tyrosinemia Type II (HT2) is a rare disorder, caused by a deficiency of tyrosine aminotransferase and is characterized by eye lesions, skin disease and/or developmental delay or intellectual deficiency. This disorder may present during infancy but may become manifest at any age
Type III (HT3) is a very rare disorder, in which only a few patients are identified¹.

TYR II are III are offered dietary management as in TYR I, but due to the lack of controlled trials and the rarity of the disorders, there is insufficient documentation on management and outcome.

Management goals in Tyrosinemia Type I:

The aim of the management of HT1 is to keep tyrosine concentrations between 200-400 μmol/l up to the age of 12 years and maintain blood phenylalanine levels in the normal range and 350-(500) μmol/l above 12 years of age.

After the age of 12 years it is common to allow the plasma tyrosine concentrations to rise modestly but the safety of this recommendation is not known and it needs to carefully monitored¹.

High tyrosine levels are a risk factor for neurotoxicity and corneal opacities. The amount of natural protein tolerated varies between patients. It has been reported to decrease from a peak of 1.8-2.4 g protein/kg/day at 4-5 months to around 1g protein/kg/day in late infancy.²

References

De Laet C, Dionisi-Vici C et al. Recommendations for the management of tyrosinaemia type I. Journal of rare diseases 2013;8:8
Dixon M, Macdonald A, White F. Disorders of amino acid metabolism, organic acidae,mias and Urea cycle disorders. In; Shaw V (ed) Clinical paediatric dietetics, 4th edn. John Wiley & Sons ltd. Sussex, 2015:381-526