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Tyrosinemia Type I
FAH gene
Tyrosinemia type I, also known as hepatorenal tyrosinemia, is a rare inborn error of tyrosine metabolism caused by mutations in the FAH gene. Clinical symptoms are highly variable even among members of the same family and affected individuals can present at any time from the neonatal period to adulthood. The disorder has been classified based on the age of onset, which broadly correlates with disease severity. The acute form typically presents prior to 6 months of age with acute liver failure. A sub-acute form manifests between 6 months and 1 year of age with liver disease, hypoglycemia, failure to thrive, coagulopathy, hepatosplenomegaly, renal Fanconi syndrome that may lead to rickets, and hypotonia. The chronic form presents after the first year of life with chronic liver disease, renal disease, rickets, cardiomyopathy and/or neurologic crises similar to porphyria. Patients with all forms have a high risk of developing hepatocarcinoma, even at a very young age. In 25 patients from various ethnic backgrounds diagnosed with Tyrosinemia type I, mutations were identified on 46/50 FAH alleles.
Tiered testing of the FAH gene is available for appropriate individuals, if requested. A mutation in intron 12 (IVS12+5 G>A) has been found in approximately 86% of patients from the province of Quebec, Canada and is homozygous in approximately 80% of patients from the Saguenay-Lac-Sainte-Jean region of Quebec. Sequencing of exon 12 and the corresponding flanking splice-sites can be requested as a first step in the analysis in appropriate individuals. Mutation analysis of the FAH gene is performed on genomic DNA from the submitted specimen using bi-directional sequence analysis of exons 1-14, and the corresponding intron/exon boundaries. If sequencing identifies a mutation on only one allele of the FAH gene, and if clinically indicated, reflex deletion/duplication testing (ExonArrayDx) will be performed at no additional charge to evaluate for a deletion/duplication of one or more exons of this gene. Mutations found in the first person of a family to be tested are confirmed by repeat analysis using sequencing, restriction fragment analysis, or another appropriate method.
Information Sheet, including prices and CPT codes
Consent Document
Genetic Test Sample Submission Form (Test Requisition Form) including Payment Options
FUMARYLACETOACETASE DEFICIENCY, FUMARYLACETOACETATE HYDROLASE, fumarate, acetoacetate, succinylacetone, AFP, alpha fetoprotein, alpha-fetoprotein, maleylacetoacetate
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