Tyrosinemia type I

Type I tyrosinemia (HT1) is the result of a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH) involved in the degradation of the amino acid tyrosine. As a result, tyrosine and methionine accumulate, as well as certain toxic substances, such as succinylacetone and succinylacetoacetate, which inhibit porphyrin metabolism. Porphyrin metabolism involves essential processes such as the synthesis of hemoglobin from red blood cells.

The prevalence of HT1 is estimated at 1 case per 100,000 population, although it is especially common in the Quebec region of Canada.

Untreated tyrosinaemia type I causes symptoms during the first year of life, the most significant of which are liver dysfunction and renal tubular dysfunction associated with growth retardation and rickets.

Renal tubular dysfunction is common in patients less than 6 months of age. Nephromegaly (kidney enlargement), rickets, growth retardation and liver cirrhosis have been observed more frequently in patients over 6 months of age, who may also develop hepatocellular carcinoma and porphyria-like symptoms.

Nitisinone (Orfadin®) is a drug approved for the treatment of type I tyrosinemia that blocks parahydroxyphenylpyruvic acid dioxygenase, the second step in the tyrosine degradation pathway, preventing the accumulation of fumarylacetoacetate;The second step in the tyrosine degradation pathway, it prevents the accumulation of fumarylacetoacetate and its conversion to succinylacetone.

Drug treatment with nitisinone should be accompanied by a diet restrictive of phenylalanine and tyrosine to prevent the formation of tyrosine crystals in the cornea. If the blood phenylalanine concentration becomes too low (20 mole/L), natural proteins should be added to the diet.

Hybrid transplantation is performed in children who have severe liver failure and do not respond to nitisinone therapy or have evidence of hepatocellular carcinoma.