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Tyrosinemia, Type I via the FAH Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9591 FAH 81406 81406,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9591FAH81406 81406,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Type I tyrosinemia (OMIM 276700) results from deficiency of fumarylacetoacetate hydrolase (FAH), the enzyme that catalyzes the final step in tyrosine catabolism. The precursor metabolite, fumarylacetoacetate, accumulates in hepatocytes in the absence of FAH activity. This results in cellular damage and diversion to succinylacetone, a reactive metabolite known to interfere with hepatic enzymes (Lindblad et al. Proc Nat Acad Sci 74:4641-4645, 1977). The first clinical signs usually appear in newborns with severe liver pathology. Biochemical findings include elevated succinylacetone in the blood and urine, elevated plasma concentrations of tyrosine, methionine, and phenylalanine, and elevated tyrosine metabolites in the urine. Some patients present after the newborn period with rickets and failure to thrive secondary to hepatic and renal dysfunction. A significant number of patients have neurological symptoms including peripheral neuropathy characterized by severe pain with extensor hypertonia, muscle weakness, paralysis requiring ventilation, and self-mutilation (Mitchell et al. N Eng J Med 322:432-437, 1990). If untreated, death usually occurs before the age of ten years, typically from liver failure, neurologic crisis, or hepatocellular carcinoma (Sniderman King et al. GeneReviews http://www.ncbi.nlm.nih.gov/books/NBK1515/). Effective treatment is achieved with nitisinone (NTBC) along with avoidance of dietary phenylalanine and tyrosine. Liver transplantation may be indicated in cases with severe liver damage or hepatocellular carcinoma (Holme et al. J Inherit Metab Dis 21:507-517, 1998).


Tyrosinemia is an autosomal recessive disorder. Variants in the FAH gene (OMIM 613871) are the genetic cause of type I tyrosinemia (OMIM #276700). Pathogenic variants include missense, nonsense, splicing, and frameshift variants. Founder variants have been identified in Ashkenazi Jewish (c.782 C>T, or p.Pro261Leu; Elpeleg et al. Hum Mut 19:80-81, 2002) and French Canadians (c.1062+5G>A; Grompe et al. N Eng J Med 331:353-357, 1994). The birth incidence of type I tyrosinemia in the USA is thought to be ~1:100,000 (Mitchell et al. in Scriver et al. (ed) The Metabolic and Molecular Basis of Inherited Disease pp.1777-1806, 2001). Higher incidences of disease in Finland and Norway result from elevated carrier rates for c.786 G>A (p.Trp262Stop) and c.1062+5G>A variants, respectively.

Clinical Sensitivity - Sequencing with CNV PGxome

Four variants (c.1062+5G>A, c.456-1G>T, c.554-6T>G, p.Pro261Leu) account for 60% of the FAH variants in the USA. p.Pro261Leu accounts for >99% of the variants in the Ashkenazi Jewish population (Elpeleg et al. Hum Mut 19:80-81, 2002) and the c.1062+5G>A accounts for nearly 90% of variants in the French Canadian population (Poudrier et al. Prenat Diagn 16:59-64, 1996).

The sensitivity of duplication/deletion testing for this rare disorder is currently unknown. However, it should be noted that at least one pathogenic gross deletion encompassing multiple FAH exons has been reported (Park, H.D. et al. Clin Chem Lab Med 47:930-933, 2009).

Testing Strategy

This test provides full coverage of all coding exons of the FAH gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients suspected of having tyrosinemia based on newborn screening or clinical features. The FAH gene may also be sequenced to determine carrier status.


Official Gene Symbol OMIM ID
FAH 613871
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Tyrosinemia Type I AR 276700

Related Test

Tyrosinemia, Type II via the TAT Gene


  • Elpeleg, O. N., et.al. (2002). "Mutation analysis of the FAH gene in Israeli patients with tyrosinemia type I." Hum Mutat 19(1): 80-1. PubMed ID: 11754109
  • Grompe, M., et.al. (1994). "A single mutation of the fumarylacetoacetate hydrolase gene in French Canadians with hereditary tyrosinemia type I." N Engl J Med 331(6): 353-7. PubMed ID: 8028615
  • Holme, E., Lindstedt, S. (1998). "Tyrosinaemia type I and NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione)." J Inherit Metab Dis 21(5): 507-17. PubMed ID: 9728331
  • Lindblad, B., et.al. (1977). "On the enzymic defects in hereditary tyrosinemia." Proc Natl Acad Sci U S A 74(10): 4641-5. PubMed ID: 270706
  • Mitchell, G., et.al. (1990). "Neurologic crises in hereditary tyrosinemia." N Engl J Med 322(7): 432-7. PubMed ID: 2153931
  • Mitchell, Grant A. et al. (2001) "Hypertyrosinemia." In: The Metabolic and Molecular Basis of Inherited Disease - 8th edition (edited by C.R. Scriver et al.) New York: McGraw-Hill.  2:1777-1806.
  • Park, H.D. et al. (2009) Clinical, biochemical, and genetic analysis of a Korean neonate with hereditary tyrosinemia type 1.  Clin Chem Lab Med 47:930-933. PubMed ID: 19569981
  • Poudrier, J., et.al. (1996). "Frequency of the IVS12 + 5G-->A splice mutation of the fumarylacetoacetate hydrolase gene in carriers of hereditary tyrosinaemia in the French Canadian population of Saguenay-Lac-St-Jean." Prenat Diagn 16(1): 59-64. PubMed ID: 8821854
  • Sniderman King, L. et.al.  "Tyrosinemia Type 1."  In: GeneReviews (edited by R.A. Pagon et al.), Seattle, 1993.   Last Updated: August 2011. PubMed ID: 20301688


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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STAT and Prenatal Test Options are not available with Patient Plus.

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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