A novel mutation causing mild, atypical fumarylacetoacetase
deficiency (Tyrosinemia type I): a case report.
In fact, nitisinone 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione, NTBC) is a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, an enzyme that is upstream of fumarylacetoacetase, and most patients present a rapid decrease in the concentrations of succinylacetone (2) when under NTBC.
Type 1 hereditary tyrosinaemia is caused by a deficiency of fumarylacetoacetate hydrolase, the enzyme responsible for the hydrolysis of fumarylacetoacetase. This latter metabolite, fumarylacetoacetase, displays mutagenic and apoptogenic activities and elicits an endoplasmic reticulum oxidative, inflammatory stress response (5).
The plasma tyrosine level has less diagnostic value than the elevated concentration of succinylacetone in the blood or urine and the reduced level of fumarylacetoacetase in the blood.
If it became practicable to measure succinylacetone or fumarylacetoacetase as part of a newborn screening program, this might lead to an improved prognosis of patients with HRT.
Preliminary clinical research studies suggest that quantitation of tyrosine in the first two days of life is extremely unreliable in ascertaining infants with tyrosinemia type 1 (fumarylacetoacetase
The primary enzyme defect has been attributed to a deficiency of fumarylacetoacetase (EC 184.108.40.206) (1).
Hereditary tyrosinemia type I: lack of correlation between clinical findings and amount of immunoreactive fumarylacetoacetase protein.
A rather small rate of false positives was observed for fumarylacetoacetase measurements by an ELISA (23).
Fumarylacetoacetase measurement as a mass screening procedure for hereditary tyrosinemia type I.
Deficiency of the enzyme fumarylacetoacetase
leads to hepatorenal tyrosinemia (type I) (85).
The primary enzyme defect in hereditary tyrosinemia type I (HT ; McKusick 276700) has been attributed to a deficiency of fumarylacetoacetase
(EC 220.127.116.11) (1).