Tyrosinemia, Type I (FAH)
Tyrosinemia, type I is an autosomal recessive disease caused by pathogenic variants in the gene FAH. While it is a pan-ethnic disease, it is identified more frequently in people of Ashkenazi Jewish or French Canadian ancestry, particularly those from the Saguenay-Lac St. Jean region of Quebec. Loss of function of the enzyme encoded by FAH causes the amino acid tyrosine to build up in the blood. The severity of the disease may vary among patients, and the most severe forms are diagnosed in infancy. These individuals have diarrhea leading to a failure to thrive, jaundice, and a cabbage-like odor of the body or urine may be noticed. Kidney failure may lead to bleeding, ascites, and sepsis, and liver disease may occur. In patients who present at an older age, liver disease and painful neurological episodes may occur. Due to cirrhosis of the liver, all patients are at an increased risk of developing hepatocellular carcinoma. No genotype-phenotype correlation has been observed, and different presentations of the disease are seen within the same family. Without treatment, life expectancy of patients with the severe form is approximately 10 years of age, but modern treatments have extended the lifespan and greatly reduced the risk of death due to cirrhosis and cancer.
For information about carrier frequency and residual risk, please see the residual risk table.