Xanthinuria Type I via the XDH 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
11863 XDH 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11863XDH81479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Xanthinuria is characterized by the accumulation of xanthine in serum and urine (Dent and Philpot, 1954. PubMed ID: 13118765; Raivio et al., 2014). Patients also present with hypouricaemia and hypouricosuria due to insufficient breakdown of xanthine (Raivio et al., 2014). Affected individuals may develop urinary xanthine calculi leading to hematuria, crystalluria, and renal colic (Bradbury et al., 1995. PubMed ID: 7577413; Carpenter et al., 1986. PubMed ID: 3755469). Clinical variability is observed and only ~50% of patients develop urolithiasis. Xanthinuria type I occasionally presents with muscle pains and cramps due to xanthine deposition (Chalmers et al., 1969. PubMed ID: 4902314; Parker et al., 1970. PubMed ID: 5414104). Xanthinuria Type II is characterized by deficiency in xanthine dehydrogenase and aldehyde oxidase due to pathogenic variants in the molybdenum cofactor sulfurase, MOCOS, gene. Although the two types have similar clinical presentation, a distinction between the two types is based on the ability to oxidize allopurinol to oxypurinol.

Genetics

Xanthinuria Type I is a rare autosomal recessive disorder caused by pathogenic variants in the XDH gene located on chromosome 2p23.1. The XDH gene encodes xanthine dehydrogenase (1333 amino acids, MW 146 kDa) which is functional as a homodimer. The xanthine dehydrogenase enzyme catalyzes two independent steps in purine metabolism: the oxidation of hypoxanthine to xanthine and xanthine to uric acid. The N-terminal 20-kDA domain contains two non-identical Fe-S clusters, the middle 40-kDa contains an FAD center, and the C-terminal 85-kDa domain binds molybdenum cofactor. Pathogenic variants include missense, nonsense, and small frameshift deletions or insertions (Arikyants et al., 2006. PubMed ID: 17115198; Eggermann et al., 2013. PubMed ID: 23249873; Ichida et al., 1997. PubMed ID: 9153281; Levartovsky et al., 2000. PubMed ID: 10844591; Nakamura et al., 2012. PubMed ID: 22981351; Sakamoto et al., 2001. PubMed ID: 11379872; Stiburkova et al., 2012. PubMed ID: 21963464; Human Gene Mutation Database). Incidence estimates range from 1 in 6,000 to 1 in 69,000 (Harkness et al., 1983. PubMed ID: 6422142; Harkness et al., 1986. PubMed ID: 3104682). This large range may reflect the rarity of the disease and population differences. Xanthinuria may be more prevalent in Mediterranean countries (Raivio et al., 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. Analytical sensitivity should be high because the great majority of pathogenic variants reported are detectable by sequencing.

Clinical sensitivity for Copy Number Variants will likely be low since only one gross deletion has been reported to date (Eggermann et al., 2013. PubMed ID: 23249873).

Testing Strategy

This test provides full coverage of all coding exons of the XDH 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

Candidates for this test are patients with plasma uric acid levels below 5 μM and plasma xanthine over 10 μM and normal metabolism of allopurinol. Testing is also indicated for family members of patients who have known XDH pathogenic variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in XDH.

Gene

Official Gene Symbol OMIM ID
XDH 607633
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Xanthinuria, Type I AR 278300

Citations

  • Arikyants et al., 2006. PubMed ID: 17115198
  • Bradbury et al., 1995. PubMed ID: 7577413
  • Carpenter et al., 1986. PubMed ID: 3755469
  • Chalmers et al., 1969. PubMed ID: 4902314
  • Dent and Philpot, 1954. PubMed ID: 13118765
  • Eggermann et al., 2013. PubMed ID: 23249873
  • Harkness et al., 1983. PubMed ID: 6422142
  • Harkness et al., 1986. PubMed ID: 3104682
  • Human Gene Mutation Database (Bio-base).
  • Ichida et al., 1997. PubMed ID: 9153281
  • Levartovsky et al., 2000. PubMed ID: 10844591
  • Nakamura et al., 2012. PubMed ID: 22981351
  • Parker et al., 1970. PubMed ID: 5414104
  • Raivio et al., 2014. Xanthine Oxidoreductase—Role in Human Pathophysiology and in Hereditary Xanthinuria. The Online Metabolic and Molecular Bases of Inherited Disease, New York, NY: The McGraw-Hill Companies, Inc.
  • Sakamoto et al., 2001. PubMed ID: 11379872
  • Stiburkova et al., 2012. PubMed ID: 21963464

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

View Ordering Instructions

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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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