Tyrosinemia: Type I

Tyrosinemia Type 1 is an inherited metabolic disorder in which the body lacks an enzyme called fumarylacetoacetate hydrolase (FAH). This enzyme is important in breaking down the amino acid tyrosine. A deficiency of FAH results in increased levels of tyrosine in blood and several different tissues and organs. There are several types of tyrosinemia, but type 1 is the most severe. Symptoms begin during the first few months of life and include failure to thrive, diarrhea, vomiting, yellowing of the skin and eyes (jaundice), an enlarged liver, and an unusual odor described as boiled cabbage smell. The kidneys, central nervous system, lungs, and bones can also be affected. If not recognized or treated promptly, tyrosinemia type 1 is usually fatal before age 10. However, with treatment and a low-tyrosine diet, approximately 90% of affected individuals will live to adulthood and experience a fairly normal life. Tyrosinemia Type 1 is caused by pathogenic variants in the FAH gene.

Tyrosinemia type 1 is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for tyrosinemia type 1. However, the risk to have a child affected with tyrosinemia type 1 is increased. Testing of reproductive partners is recommended for carriers of tyrosinemia type 1.

Tyrosinemia type 1 affects approximately 1 in 100,000 to 1 in 120,000 newborns worldwide. The disease is more common in Norway, Finland, and Quebec. The highest occurance of the disorder is in the Saguenay-Lac-Saint-Jean region of Quebec, Canada, with 1 in 1,846 affected newborns.

Genetic Home Reference: Tyrosinemia Type 1 (http://ghr.nlm.nih.gov/)
Genetic Alliance: Tyrosinemia Type 1 (http://www.diseaseinfosearch.org/)

OMIM [Tyrosinemia Type 1: 276700] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Tyrosinemia Type 1-related disorders (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing