Tyrosinemia type III
Tyrosinemia is inherited in an autosomal recessive pattern. Normally a person has two functional HPD genes. In people with tyrosinemia type III, both of these genes have a mutation and there is a deficiency of the HPD enzyme. Each parent of a newborn with tyrosinemia type III typically has one functional and one mutated HPD 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 lll do not typically have symptoms.
The symptoms of tyrosinemia type III are variable, but may include intellectual disability, seizures, and intermittent ataxia. Some individuals are asymptomatic. There is no liver, ocular or skin involvement in tyrosinemia type III.
- Incidence: Tyrosinemia type III is rare, with an estimated incidence of less than 1 in 1,000,000.
- New York State Method of Screening (First Tier): Screening for tyrosinemia type III 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 III 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 HPD gene testing.
Management requires dietary restriction of phenylalanine and tyrosine. Vitamin C supplementation may be beneficial as well.
Many individuals with tyrosinemia type III are asymptomatic, particularly when diet is started early. Children with the condition do have a risk of intellectual disability.
Tyrosinemia type III is characterized by elevated blood levels of the amino acid tyrosine. Tyrosine is a building block of many proteins. Tyrosinemia type III is caused by a deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPD), one of the enzymes required to break down tyrosine. The HPD gene provides instructions for making the HPD enzyme; mutations in this gene cause dysfunction and therefore tyrosine is not broken down. Toxic metabolites accumulate and cause symptoms.