Geographical and Ethnic Distribution of Mutations of the Fumarylacetoacetate Hydrolase Gene in Hereditary Tyrosinemia Type 1

JIMD Rep. 2015:19:43-58. doi: 10.1007/8904_2014_363. Epub 2015 Feb 15.


Hereditary tyrosinemia type 1 (HT1) (OMIM 276700) is a severe inherited metabolic disease affecting mainly hepatic and renal functions that leads to a fatal outcome if untreated. HT1 results from a deficiency of the last enzyme of tyrosine catabolism, fumarylacetoacetate hydrolase (FAH). Biochemical findings include elevated succinylacetone in blood and urine; elevated plasma concentrations of tyrosine, methionine and phenylalanine; and elevated tyrosine metabolites in urine. The HT1 frequency worldwide is about 1 in 100,000 individuals. In some areas, where the incidence of HT1 is noticeably higher, prevalence of characteristic mutations has been reported, and the estimated incidence of carriers of a specific mutation can be as high as 1 out of 14 adults. Because the global occurrence of HT1 is relatively low, a considerable number of cases may go unrecognized, underlining the importance to establish efficient prenatal and carrier testing to facilitate an early detection of the disease. Here we describe the 95 mutations reported so far in HT1 with special emphasis on their geographical and ethnic distributions. Such information should enable the establishment of a preferential screening process for mutations most predominant in a given region or ethnic group.