Porphyria Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10255 ALAD 81479,81479 Order Options and Pricing
ALAS2 81479,81479
CPOX 81405,81479
FECH 81479,81479
HMBS 81406,81479
PPOX 81406,81479
UROD 81479,81479
UROS 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10255Genes x (8)81479 81405, 81406, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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.

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

Porphyrias are a group of metabolic disorders caused by impairment of the heme biosynthesis pathway. There are two different forms of porphyria: acute/neurovisceral and chronic/cutaneous. Symptom onset typically occurs in late childhood to adulthood. Acute porphyrias include acute intermittent porphyria (AIP), variegate porphyria (VP), ALA dehydratase prophyria (ADP) and hereditary coproporphyria (HCP). These disorders involve episodic nervous system attacks often resulting in abdominal pain, and psychiatric and neurologic effects. In severe cases attacks can be life threatening resulting in peripheral motor neuropathy, seizures, coma, or bulbar paralysis.

Chronic porphyrias include congenital erythropoietic porphyria (CEP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), hereditary coproporphyria (HCP) variegate porphyria (VP), erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP). In these patients, either blistering or non-blistering cutaneous lesions occur at sites of sun exposure.

PCT is the most common form of porphyria with an occurrence of 1 in 10,000 in Europeans. AIP and EPP are found in 1 in 20,000 and 1 in 50,000 Europeans respectively (Karim et al. 2015; Besur et al. 2014). Acute and chronic specific porphyria panels as well as individual porphyria gene testing are also available.

Genetics

There are currently eight different forms of porphyria caused by specific pathogenic variants in genes involved in heme biosynthesis: ALA dehydratase porphyria (ALAD), acute intermittent porphyria (HMBS), hereditary coproporphyria (CPOX), variegate porphyria (PPOX), porphyria cutanea tarda/hepatoerythropoietic porphyria (UROD), congenital erythropoietic protoporphyria (UROS), erythropoietic protoporphyria (FECH), and X-linked protoporphyria (ALAS2).

Autosomal dominant forms of porphyria include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria cutanea tarda. Autosomal recessive forms include ALA dehydratase porphyria, hepatoerythropoietic porphyria, congenital erythropoietic protoporphyria and erythropoietic protoporphyria. Only pathogenic variants in the ALAS2 gene are involved in an X-linked recessive form of porphyria (Karim et al. 2015; Besur et al. 2014).

See individual gene test descriptions for information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

Detection of pathogenic variants in the FECH gene was found in 140 of 151 patients with protoporphyia with the remaining 11 demonstrating X-linked forms through pathogenic variants in the ALAS2 gene (Balwani et al. 2013). Analytical sensitivity is ~90% as gross deletions cannot be detected by this method and are responsible for ~10% of cases (Whatley et al. 2007; Gouya et al. 2006).

In a series of 103 patients where variegate porphyria diagnosis was established by elevated fecal porphyrin measurement, decreased PPOX activity, and elevated plasma porphyrin fluorescence, pathogenic variants were identified in 96% of cases (Whatley et al. 1999). Analytical sensitivity is >95% for detection of pathogenic variants in the PPOX gene (Singal and Anderson 1993).

In two studies with individuals having a clinical and biochemical diagnosis of hereditary coproporphyria, pathogenic variants in the CPOX gene were identified in 29 of 31 and 32 of 32 patients respectively (Whatley et al. 2009; Rosipal et al. 1999). Analytical sensitivity is >95% as gross deletions in the CPOX gene have only been reported in rare cases (Whatley et al. 2009).

In a series of unrelated patients with congenital erythropoietic porphyria, pathogenic variants in the UROS gene were identified in 24 of 27 cases (Katugampola et al. 2012). Analytical sensitivity is >99% as all reported variants are detectable by this method. Only one case of a gross deletion encompassing exons 2-3 in the UROS gene has been reported (Katugampola et al. 2012).

In a patient cohort containing both sporadic and familial porphyria cutanea tarda, pathogenic variants in the UROD gene were identified in 131 of 248 patients (Aarsand et al. 2009). Analytical sensitivity is >95% as large deletions cannot be detected by this method and have only been reported in a few cases (Mendez et al. 1998; Liu et al. 2013).

In patients with decreased PBG activity indicative of acute intermittent porphyria, underlying pathogenic variants in the HMBS gene were detected in 240 of 252 individuals (Puy et al. 1997). Analytical sensitivity for detection of causative variants in the HMBS gene is >95% as large deletions are present in only a few cases (Whatley et al. 2009).

Analytical sensitivity for the ALAD gene should be high as all pathogenic variants reported are detectable by sequencing. Clinical sensitivity cannot be estimated because of the small number of patients reported to date.

Gross deletions have been reported in <10% of erythropoietic protoporphyria cases (FECH gene), <5% of variegate porphyria cases (PPOX gene), <5% of hereditary coproporphyria cases (CPOX gene), <2% of congenital erythropoietic porphyria cases (UROS gene), <5% of porphyria cutanea tarda cases (UROD gene), and <5% of acute intermittent porphyria cases (HMBS gene). To date, gross deletions/duplications have not been reported in the ALAD or ALAS2 genes.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 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

Patients presenting with unexplained neurovisceral attacks including vomiting, abdominal pain, psychiatric and neurological effects are indicative of acute forms of porphyria. Blistering on sun exposed areas is a typical feature of patients with chronic/cutaneous porphyria. Ideal candidates for testing have biochemical evidence indicating elevated levels of specific porphyrins in urine, plasma, erythrocytes, and/or feces (Karim et al. 2015; Besur et al. 2014).

Genes

Official Gene Symbol OMIM ID
ALAD 125270
ALAS2 301300
CPOX 612732
FECH 612386
HMBS 609806
PPOX 600923
UROD 613521
UROS 606938
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Aarsand A.K. et al. 2009. Clinical Chemistry. 55: 795-803. PubMed ID: 19233912
  • Balwani M. et al. 2013. X-Linked Protoporphyria. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 23409301
  • Besur S. et al. 2014. Metabolites. 4: 977-1006. PubMed ID: 25372274
  • Gouya L. et al. 2006. American Journal of Human Genetics. 78: 2-14. PubMed ID: 16385445
  • Karim Z. et al. 2015. Clinics and Research in Hepatology and Gastroenterology. 39: 412-25. PubMed ID: 26142871
  • Katugampola R.P. et al. 2012. The British Journal of Dermatology. 167: 901-13. PubMed ID: 22816431
  • Liu L.U. et al. 2013. Porphyria Cutanea Tarda, Type II. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 23741761
  • Mendez M. et al. 1998. American Journal of Human Genetics. 63: 1363-75. PubMed ID: 9792863
  • Puy H. et al. 1997. The American Journal of Human Genetics. 60: 1373–83. PubMed ID: 9199558
  • Rosipal R. et al. 1999. Human Mutation. 13: 44-53. PubMed ID: 9888388
  • Singal A.K. et al. 1993. Variegate Porphyria. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 23409300
  • Whatley S.D. et al. 1999. American Journal of Human Genetics. 65: 984-94. PubMed ID: 10486317
  • Whatley S.D. et al. 2007. The Journal of Investigative Dermatology. 127: 2790-4. PubMed ID: 17597821
  • Whatley S.D. et al. 2009. Clinical Chemistry. 55: 1406-14. PubMed ID: 19460837

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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