These results demonstrate the strong selective advantage of FAH-expressing cells in an FAH-deficient liver but also illustrate the danger of carcinomas arising from FAH-deficient hepatocytes in HT1.
A high level of succinylacetone (SA) in blood is a sensitive, specific newborn screening marker for hepatorenal tyrosinemia type 1 (HT1, MIM 276700) caused by deficiency of fumarylacetoacetate hydrolase (FAH).
The patient, currently aged 12 years, shows a normal physical and psychomotor development.This is the first report of mild tyrosinemia type I disease caused by an Ala35Thr mutation in the FAH gene, presenting atypically without increase of the diagnostically important toxic metabolites succinylacetone and succinylacetoacetate.
To investigate the molecular heterogeneity of tyrosinemia, the geographic distribution and the genotype-phenotype relationship, we have analyzed the FAH genotype of 25 HT1 patients.
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.
The finding that the Fah gene in wild-type mice is highly expressed only in cell types that develop a phenotype in mutants, and the fact that Fah deficiency determines the human liver disease hereditary tyrosinemia type 1 (HT1), suggested that disruption of the Fah gene was responsible for the lethal albino phenotype.
Recently, we identified a splice mutation and two nonsense mutations in the fumarylacetoacetate hydrolase gene in two patients from Quebec with tyrosinemia type I.