Tyrosinemia is inherited in an autosomal recessive pattern. Normally a person has two functional TAT genes. In people with tyrosinemia type II, both of these genes have a mutation and there is a deficiency of the TAT enzyme. Each parent of a newborn with tyrosinemia type II typically has one functional and one mutated TAT 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 ll do not typically have symptoms.
The symptoms of tyrosinemia type II include painful skin lesions (palmoplantar hyperkeratosis of the hands and feet) and ocular manifestations such as red eyes, photophobia, excessive tearing and pain, corneal clouding and ulceration, and pseudodendritic keratitis. The ocular features of tyrosinemia type II may affect vision. Ocular symptoms usually present first, most often in the first year of life. Skin symptoms usually appear after a year of age. Central nervous system involvement is less common, but can include intellectual disability, behavioral problems, nystagmus, tremors, ataxia and/or convulsions. There is no liver involvement in tyrosinemia type II.
- Incidence: The incidence of tyrosinemia type II is less than 1 in 250,000. It appears to be more common in individuals of Mediterranean and/or Arab descent.
- New York State Method of Screening (First Tier): Screening for tyrosinemia type II is accomplished by measuring tyrosine by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: Prematurity, vitamin C deficiency, or high protein intake. Supplementation with total parenteral nutrition can cause a false positive screen.
- 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 II 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 plasma amino acids, urine organic acids and TAT gene testing.
Management requires dietary restriction of phenylalanine and tyrosine. A controlled diet results in reduction of plasma tyrosine levels and quick resolution of skin and ocular manifestations. It is unclear how much, or if, the diet affects central nervous system involvement. Oral retinoids may be helpful in treatment of the skin lesions.
Oculocutaneous manifestations quickly resolve when individuals with tyrosinemia type II restrict dietary consumption of phenylalanine and tyrosine.
Tyrosinemia type II is characterized by elevated blood levels of the amino acid tyrosine. Tyrosine is a building block of many proteins. Tyrosinemia type II is caused by a deficiency of tyrosine aminotransferase (TAT), one of the enzymes required to break down tyrosine. The TAT gene provides instructions for making the TAT enzyme; mutations in this gene cause dysfunction and therefore tyrosine is not broken down. Toxic metabolites accumulate and cause symptoms.