Introduction and background - TYR I

Tyrosinemia Type I (HT1) is an inborn error of metabolism, characterized by a deficiency of the enzyme, fumarylacetoacetate hydrolase, which occurs in the final step of the Tyrosine degradation pathway. This enzyme deficiency results in accumulation of toxic metabolites.

Tyrosine is a non-essential amino acid present in natural protein and also endogenously synthesized from the hydroxylation of phenylalanine. Tyrosine is needed for body protein synthesis and is a precursor for the synthesis of catecholamine’s, thyroid hormones and melanin.

HT1 can present clinically at any age from infancy to adulthood. It can manifest with a variety of clinical symptoms and severity which usually classified by the severity of the disease

No symptoms at birth
Acute – the most common form presents before 6 months of age with acute liver failure, the most severe before 2 months after birth
Sub-acute form – presents between 6 months and 1 year of age with progressive liver failure, hepatosplenomegaly, coagulopathy, faltering growth and rickets
Chronic – presents over 1 year of age with chronic liver or renal disease and rickets or with porphyria like episodes; some may also have cardiomyopathy

The management of HT1 has been revolutionized by the introduction of the drug Nitisinone, but dietary restriction of tyrosine (TYR) and phenylalanine (PHE) is still essential and consequently several management guidelines have been published in HT1 in the past years.

In HT1, the main management principle is to reduce tyrosine levels by early institution of restricted dietary PHE and TYR intake, by restriction of protein containing foods. Additionally phenylalanine and tyrosine-free L-amino acid supplement must be provided to compensate for the resulting deficiencies in the other essential and non-essential amino acids and micronutrients. This dietary management of Tyrosinemia has shown to be essential to optimize outcome and avoid the potential consequences of poor metabolic control.

Early diagnosis of Tyrosinemia through New Born Screening (NBS) in the first days of life is now established in several countries, but not widely available in the world because of the rarity of the disease. If immediate initiation of Nitisonone and appropriate dietary intervention is initiated, it will prevent children with HT1 from damage to the main organs, such as liver dysfunction, chronic renal disease, growth failure and damage to peripheral nerves.

HT1 has a birth incidence of approximately 1 in 100.000-120.000 in most area’s but is more common in some regions, notably in Quebec, Canada (1:16.000), Norway and Finland (1:60.000).

Nutricia supports ‘diet for life’ for all patients with Tyrosinemia. Research has shown that adherence to a well-managed diet plan provides the best possible clinical outcomes in these patients.

References

Holme E, Mitchell GA. Tyrosine metabolism In; Blau N (ed) Physician’s guide to the diagnosis, treatment and follow-up of inherited metabolic diseases, 2nd edn. Springer Heidelberg, 2014:23-33
Van Spronsen FJ, Thomasse Y et al. Hededitary tyrosinemia type I: a new clinical classification with difference in prognosis on dietary treatment 1994;20(5):1187-1191
De Laet C, Dionisi-Vici C et al. Recommendations for the management of tyrosinaemia type I. Journal of rare diseases 2013;8:8
El-Shabrawi MH, Kamal NM, Current management options for tyrosinemia. Orphan drugs: Research a

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