Hereditary tyrosinaemia type I in Norway: Incidence and three novel small deletions in the fumarylacetoacetase gene

Abstract

A total of 28 Norwegians have been diagnosed with hereditary tyrosinaemia type I (HT1) over the last 30 years. In this study, 19 of these patients were investigated. Three novel small deletions were found (NM_000137.1(FAH): c.615delT, p.Phe205LeufsX2, NM_000137.1(FAH): c.744delG, p.Pro249HisfsX55 and NM_000137.1(FAH):c835delC) pGln279ArgfsX25, all of them leading to a change in the reading frame and a premature stop codon. We hereby genetically characterized 51 of the 56 disease-causing alleles, identifying nine different disease-causing mutations in the Norwegian population. We found that 65% of the Norwegian HT1 patients are compound heterozygous for different mutations. Thus, the relatively high incidence of HT1 in Norway of 1 in 74,800 live births is not due to single founder effects or high incidence of parental consanguinity.

Key Words::

• Inborn errors of metabolism
• metabolic disease
• single gene disorders
• amino acids
• epidemiology
• genotype
• frameshift mutation
• liver disease
• hepatocellular carcinoma

Acknowledgements

We would like to thank Lars Mørkrid for help with statistical analyses and Anne Marie Lund, Gro Guldal and Kari Høie for technical assistance.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.