Tyrosinemia type I

Tyrosinemia type 1 is a serious recessive condition caused by an enzyme deficiency. It is extremely rare, occurring in about 1 in 100,000 people worldwide, but in 1 in 2,000 among some French-Canadian populations. [1]

Type 1 disease is caused by mutations in the fumarylacetoacetase (FAH) gene. Carriers with a single mutated copy of the gene are not affected. Other types of tyrosinemia are caused by defects in the 4-hydroxyphenylpyruvate dioxygenase (HPD) and tyrosine aminotransferase (TAT) genes.

Some Relevant SNPs

SNPs associated with tyrosinemia type 1 include:

• rs121965075 or i5012864; E357X; risk allele T in both dbSNP and 23andMe
• rs80338899 or i5012862; W262X; risk allele A in both dbSNP and 23andMe
• rs80338898 or i5012861; P261L; risk allele T in both dbSNP and 23andMe
• rs80338897 NM_000137.2(FAH):c.698A>T (p.Asp233Val)
• rs80338896 NM_000137.2(FAH):c.607-6T>G
• rs80338895 NM_000137.2(FAH):c.554-1G>T
• rs80338894 NM_000137.2(FAH):c.192G>T (p.Gln64His)
• rs80338901 or i5012865; IVS12+5G>A; risk allele A in both dbSNP and 23andMe
• rs80338900 NM_000137.2(FAH):c.1009G>A (p.Gly337Ser)
• rs80338895 or i5012867; IVS6-1G>T; risk allele T in both dbSNP and 23andMe
• rs11555096 NM_000137.2(FAH):c.1021C>T (p.Arg341Trp)

See List of variants reported as pathogenic for Tyrosinemia type I by Gene Reviews [2]

An apparently less severe form of tyrosinemia type 1 caused by a novel mutation in the FAH gene was reported in 2009 in a Belgian infant. [PMID 20003495]

• 103G>A (Ala35Thr), which in GRCh38, is at position 80158081 (ch 15) but currently lacks an entry in dbSNP

Publications

[PMID 30414057] The Unique Spectrum of Mutations in Patients with Hereditary Tyrosinemia Type 1 in Different Regions of the Russian Federation.

[PMID 28771246] Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations.

[PMID 25681080] Geographical and Ethnic Distribution of Mutations of the Fumarylacetoacetate Hydrolase Gene in Hereditary Tyrosinemia Type 1.

[PMID 23311542] Recommendations for the management of tyrosinaemia type 1.

[PMID 17997497] Hereditary tyrosinaemia type I: from basics to progress in treatment.