What Is Tyrosinemia?
Tyrosinemia is an inherited disorder that has three different forms: type 1, type II, and type III. In each case, the disorder is marked by the body's inability to break down the amino acid tyrosine found in virtually every protein that we consume. If tyrosinemia is left untreated, tyrosine levels can elevate to the point that they become very harmful.
Each one of the three types of tyrosinemia has its own hallmark symptoms. The type I form, the most severe of the three forms, is marked by symptoms that usually first appear shortly after birth. These symptoms include the failure to maintain a healthy body weight (infants are underweight), jaundice (yellowing of the skin and eyes), vomiting, and increased susceptibility to bleeding. If left untreated, type I tyrosinemia can lead to other severe symptoms, such as organ failure, susceptibility to developing liver cancer, and nervous system anomalies, for example.
In the type II form of tyrosinemia, affected individuals typically experience eye, skin, and mental problems. These symptoms include, but are not limited to, excess watering and redness of the eyes, skin lesions and rashes, and, in about one-half of all cases, reduced cognitive skills. Unlike the type I form, the type II form usually first presents well after infancy, and usually in later childhood.
Symptoms common to type III tyrosinemia include seizures, balance problems, and decreased intellectual function. Type III is by far the rarest of the three forms of tyrosinemia as only a handful of individuals have ever been diagnosed with this form whereas the type I form affects about 1 person in every 100,000 and the type II form strikes at an incidence of about 1 in every 250,000.
What Is Known About The Genetic Causes Of Tyrosinemia?
As there are three distinct forms of tyrosinemia, it should come as little surprise that human molecular geneticists have determined that each one is caused by mutation to one of three different genes. Specifically, tyrosinemia results in individuals who have one or mutations in both copies of any one of the three genes that are referred to as FAH (type I), HPD (type II), and TAT (type III). The FAH, HPD, and TAT genes all encode a different protein. In each case, the protein is necessary, in one of three distinct steps, for the proper break down of tyrosine. Individuals who have a mutation in both copies of one of these genes therefore cannot properly process tyrosine, which leads to its accumulation in the body, and ultimately to the symptoms described in the previous section.
This article is only meant to provide some basic information regarding the genetic condition known as tyrosinemia. If you have any further questions regarding this inherited disorder and its treatment options, please contact your doctor or consult a genetic counselor.
Genetics Home Reference, National Institutes of Health, FAH: https://ghr.nlm.nih.gov/gene/FAH
Genetics Home Reference, National Institutes of Health, HPD: https://ghr.nlm.nih.gov/gene/HPD
Genetics Home Reference, National Institutes of Health, TAT: https://ghr.nlm.nih.gov/gene/TAT
Genetics Home Reference, National Institutes of Health, Tyrosinemia: https://ghr.nlm.nih.gov/condition=tyrosinemia
L.S. King et al., GeneReviews, University of Washington, Tyrosinemia Type I: https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tyrosinemia