Test Code APGP Acute Porphyria Gene Panel, Varies

Ordering Guidance

Customization of this panel and single gene analysis for any gene present on this panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.

Submit only 1 of the following specimens:

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

Specimen Type: Cultured fibroblast

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection Filter Paper (T493)

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or blood spot collection card

Specimen Volume: 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information:

1. Due to lower concentration of DNA yielded from blood spots, it is possible that additional specimen may be required to complete testing.

2. For collection instructions, see Blood Spot Collection Instructions.

3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777).

4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800).

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527)

3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Secondary ID

608015

Useful For

Establishing a molecular diagnosis for patients with acute porphyria

Identifying variants within genes known to be associated with acute porphyria, allowing for predictive testing of at-risk family members

Disease States

Porphyria

Testing Algorithm

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

The following algorithms are available:

-Porphyria (Acute) Testing Algorithm

-Porphyria (Cutaneous) Testing Algorithm

Special Instructions

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

Acute Porphyria Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type	Temperature	Time	Special Container
Varies	Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Acute porphyria is caused by variants in 1 of 4 genes:

-HMBS is associated with acute intermittent porphyria (AIP)

-CPOX is associated with hereditary coproporphyria (HCP)

-PPOX is associated with variegate porphyria (VP)

-ALAD is associated with aminolevulinic acid dehydratase deficiency porphyria

Variants in these genes show incomplete penetrance, and patients with a confirmed deleterious variant may be asymptomatic.

Clinical manifestations of acute porphyria include attacks of neurologic dysfunction, commonly characterized as abdominal pain. However, these acute attacks are variable and can include vomiting, diarrhea, constipation, urinary retention, acute episodes of neuropathic symptoms, psychiatric symptoms, seizures, respiratory paralysis, tachycardia, and hypertension. Respiratory paralysis can progress to coma and death.

HCP and VP are also associated with cutaneous manifestations, including edema, sun-induced erythema, acute painful photodermatitis, and urticaria. In some cases, patients present with isolated photosensitivity.

Acute attacks may be prevented by avoiding both endogenous and exogenous triggers. These triggers include porphyrogenic drugs, hormonal contraceptives, fasting, alcohol, tobacco, and cannabis.

Fecal porphyrins and quantitative urinary porphyrins analyses are helpful in establishing a diagnosis of acute porphyria.

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated to be over 99% for single nucleotide variants, over 94% for deletions-insertions (delins) less than 40 base pairs (bp), and over 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Acute Porphyria Gene Panel for details regarding the targeted genes analyzed and the specific gene regions not routinely covered.(Unpublished Mayo method)

Genes analyzed: ALAD, CPOX, HMBS, and PPOX

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81405

81406 x 2

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

81479 (if appropriate for government payers)

LOINC Code Information

Test ID	Test Order Name	Order LOINC Value
APGP	Acute Porphyria Gene Panel	105344-6

Result ID	Test Result Name	Result LOINC Value
608584	Test Description	62364-5
608585	Specimen	31208-2
608586	Source	31208-2
608587	Result Summary	50397-9
608588	Result	82939-0
608589	Interpretation	69047-9
608590	Resources	99622-3
608591	Additional Information	48767-8
608592	Method	85069-3
608593	Genes Analyzed	48018-6
608594	Disclaimer	62364-5
608595	Released By	18771-6

Day(s) Performed