Tyrosinemia Type I results from deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). Typical biochemical findings include increased plasma and urine concentration of succinylacetone, elevated plasma concentrations of tyrosine, methionine, and phenylalanine, and elevated urinary concentration of tyrosine metabolites.
FAH enzyme is encoded by the FAH gene located at 15q23, and mutations to this gene are responsible for tyrosinemia by leading to reduced or absent FAH enzyme activity. The four common FAH mutations (IVS12+5 G>A, IVS6-1 G>T, IVS7-6 T>G, P261L) account for approximately 60% of mutations in tyrosinemia type I in the general US population. The P261L mutation accounts for nearly 100% of mutations responsible for tyrosinemia type I in the Ashkenazi Jewish population . IVS12+5 G>A accounts for 87.9% of mutations in the French Canadian population . However, no genotype/phenotype correlation has been established . Gene sequence analysis is available to test for mutations in the FAH gene. (EU). For patients with mutations not identified by full gene sequencing, a separate deletion/duplication assay is available using a targeted CGH array (EV).
- Confirmation of a clinical/biochemical diagnosis of Tyrosinemia Type I.
- Carrier testing in adults with a family history of Tyrosinemia Type I.
Targeted CGH Array: DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.
Clinical Sensitivity: 52/58 mutations identified in 29 patients , 47/50 mutations identified in 25 patients .
Analytical Sensitivity: ~99%
Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
- Plasma Amino Acid Analysis (AA) and Urine Organic Acids (OA) including succinylacetone and tyrosine metabolites.
- Custom Diagnostics Known Mutation Analysis (KM) is available to family members if mutations are identified by sequencing.
- Tyrosinemia Type I Deletion/Duplication Assay (EV) is available separately for individuals where mutations are not identified by sequence analysis. Refer to the test requisition or contact the laboratory for more information.
- Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.