Tyrosinemia type I
Tyrosinemia is inherited in an autosomal recessive pattern. Normally a person has two functional FAH genes. In people with tyrosinemia type I, both of these genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with tyrosinemia type l typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of tyrosinemia type l do not typically have symptoms.
The symptoms of tyrosinemia begin in the newborn period or in the first year of life. The symptoms impact many systems of the body including the liver, the kidneys and the nervous system. The liver symptoms may include liver failure and liver cancer (hepatocellular carcinoma). Untreated liver disease can cause increased bleeding, jaundice and a cabbage-like body odor. The renal disease is called renal tubular dysfunction and causes loss of nutrients in the urine. The neurological symptoms occur as a crisis with change in mental status, abdominal pain and respiratory failure.
- Incidence: The incidence of tyrosinemia type l is about 1 in 100,000 to 1 in 120,000 births. It is more common in people from Norway, French Canada (Quebec) and Finland.
- New York State Method of Screening (First Tier): Screening for tyrosinemia, type I is accomplished by measuring succinylacetone by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: None known
- Interpretation/reporting of data: Results are reported as screen negative, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for tyrosinemia type l are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of tyrosinemia.
Diagnostic testing may include liver function testing, plasma amino acids, succinylacetone, urine organic acids and FAH gene testing.
Treatment usually includes a medication, Nitisitone, and a low tyrosine diet. For severe cases, a liver transplant may be considered.
On treatment, prognosis is significantly improved and the survival rate is higher than 90%. Some forms may not respond to medication.
Multiple steps in the body are required to breakdown components of protein (amino acids) tyrosine, methionine and phenylalanine. The FAH gene provides instructions for an important enzyme in this process, fumarylacetoacetate hydrolase. If there are mutations in this gene, the enzyme does not function and the amino acids are not broken down. Toxic metabolites accumulate and cause symptoms.