Diagnostic tardif de la tyrosinémie héréditaire de type I, le cas de deux faux jumeaux

Abstract

AbstractHereditary tyrosinemia type 1 (TH1) is an autosomal recessive inherited aminoacidopathy caused by a deficiency of an enzyme involved in the last step of tyrosine catabolism called fumarylacetoacetate hydrolase (FAH). The accumulation of metabolites fumarylacetoacetate, succinylacetoacetate and succinylacetone generates renal and hepatic toxicity, hence the name hepatorenal tyrosinemia. In the context of targeted screening, two male fraternal twins of consanguineous parents and with a history of death in the siblings, as well as a cousin, were diagnosed for TH1. The dosage of urinary succinylacetone (SA) came back for the first twin in favor of tyrosinemia, but the dosage in the second twin was positive only after the fourth determination confirming the pathology diagnosis. Classically, the SA rate rises from the first days of life; the heterogeneity of the mutations affecting the FAH gene can explain this phenotypic fluctuation also the action of modulating factors still little known without any reported correlation between the genotype and the phenotype. The genetic study revealed a frequent genetic mutation of the FAH gene.