Tyrosinemia, Type II via the TAT 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
9791 TAT 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9791TAT81479 81479 $890 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.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Tyrosinemia Type II, also known as Oculocutaneous Tyrosinemia or Richner-Hanhart syndrome, results from a deficiency of cytosolic hepatic tyrosine aminotransferase (TAT), the enzyme that catalyzes the first step in tyrosine catabolism (Natt et al. 1992; Mitchell et al. 2014). Affected patients present with eye, skin and neurologic symptoms. Typically, the ocular symptoms are the first to appear and are usually observed during the first year of life. These symptoms most frequently include lacrimation, photophobia, redness and pain, as well as dendritic corneal erosions that stain poorly or not at all with fluorescein. Approximately 75% of affected patients manifest such ocular symptoms. Skin abnormalities, which affect approximately 80% of patients and usually arise after the first year of life, are most commonly painful palmoplantar keratoderma. TAT deficient patients may present with only skin or eye symptoms, or with both. Lastly, over 60% of affected patients present with intellectual disability, which can range from a mild decrease in intelligence to severe intellectual disability associated with microcephaly and other organ abnormalities (Charfeddine et al. 2006; Mitchell et al. 2014). Biochemically, these patients are found to have greatly increased plasma and urine concentrations of tyrosine and its derivatives. It is important to note that TAT deficiency can be distinguished biochemically from fumarylacetoacetate hydrolase (FAH) deficiency (Tyrosinemia Type I) because urinary succinylacetone is not elevated in TAT deficient patients as it is in FAH deficient patients (Mitchell et al. 2014).

Effective treatment for these patients is dietary restriction of phenylalanine and tyrosine. In patients already presenting with skin and eye abnormalities, dietary restriction can reverse existing problems. However, dietary changes have not been shown to be effective at reversing cognitive impairment. Therefore, it is essential that TAT deficient patients are diagnosed early so that dietary changes can be implemented prior to the onset of intellectual disability (Natt et al. 1992; Mitchell et al. 2014).

Genetics

Tyrosinemia Type II is an autosomal recessive disorder, and TAT is the only gene in which defects are known to cause TAT deficiency. To date, over 20 causative variants have been reported in the TAT gene. The majority of reported variants are missense, although nonsense, frameshift, splice site, indels and gross deletions have all been reported (Human Gene Mutation Database). Pathogenic variants have been identified throughout the length of the gene, but most reported variants are found in the last coding exon.

TAT deficiency is caused by defects in the tyrosine aminotransferase enzyme, which is the first enzyme in the tyrosine catabolic pathway and is responsible for the conversion of tyrosine to 4-hydroxyphenylpyruvate. A defect in this enzyme results in the accumulation of tyrosine and its metabolites, although a direct causal link between hypertyrosinemia and the associated phenotype has not yet been established (Mitchell et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity is difficult to estimate because only a small number of patients have been reported. Analytical sensitivity should be high because the great majority of variants reported are detectable by direct sequencing.

To date, very few gross deletions or insertions have been reported in the TAT gene (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the TAT 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Individuals with increased urinary and plasma tyrosine levels, but normal concentrations of succinylacetone are good candidates for this test, as are patients with clinical symptoms suggestive of TAT deficiency. Family members of patients who have known TAT variants are candidates. We will also sequence the TAT gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
TAT 613018
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Tyrosinemia Type 2 AR 276600

Related Test

Name
Tyrosinemia, Type I via the FAH Gene

Citations

  • Charfeddine C. et al. 2006. Molecular Genetics and Metabolism. 88: 184-91.  PubMed ID: 16574453
  • Human Gene Mutation Database (Bio-base).
  • Mitchell GA et al. 2014. Hypertyrosinemia. In: Valle D, Beaudet A.L., Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.
  • Natt E. et al. 1992. Proceedings of the National Academy of Sciences of the United States of America. 89: 9297-301.  PubMed ID: 1357662

Ordering/Specimens

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.

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

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ORDER OPTIONS

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2) Select Additional Test Options

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

No Additional Test Options are available for this test.

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