Abstract
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.
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Competing interests: None declared
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- BCH:
-
Birmingham Children’s Hospital
- FAH:
-
Fumarylacetoacetate hydrolase
- GTR:
-
Genetic Testing Registry
- HCC:
-
Hepatocellular carcinoma
- HT1:
-
Hereditary tyrosinemia type 1
- LGCD:
-
Laboratory of Cell and Developmental Genetics
- NTBC:
-
2-(2-Nitro-trifluoromethylbenzoyl) 1,3-cyclohexanedione
- SLSJ:
-
Saguenay-Lac-St-Jean region
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Acknowledgements
Work on HT1 was supported by the Canadian Institutes for Health Research (grant to RMT, studentship to AB and postdoctoral fellowship to FA).
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Communicated by: Bridget Wilcken
Appendices
Synopsis
Geographical and ethnic distribution of mutations in hereditary tyrosinemia type 1
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Francesca Angileri, Anne Bergeron, Geneviève Morrow, Francine Lettre, George Gray, Tim Hutchin, Sarah Ball and Robert M. Tanguay declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration as revised in 2013.
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This article does not contain any studies with animal subjects performed by any of the authors.
Author’s Contributions
AB and FA contributed equally to this review. AB, FA and SB did the literature review and contributed to the draft of the manuscript. FL, TH and SB performed mutational analysis in some patients. RMT, GM and GG designed the review and worked on the draft of the manuscript. All authors read and approved the final manuscript.
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Angileri, F. et al. (2014). Geographical and Ethnic Distribution of Mutations of the Fumarylacetoacetate Hydrolase Gene in Hereditary Tyrosinemia Type 1. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 19. JIMD Reports, vol 19. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_363
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