Test Catalog

Test Id : FECHZ

Ferrochelatase (FECH) Gene, Full Gene Analysis, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirmation of a diagnosis of erythropoietic protoporphyria (EPP) following positive biochemical genetic test results obtained through PEE / Porphyrins Evaluation, Whole Blood

 

Carrier testing for individuals with a family history of EPP in the absence of known mutations in the family

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Porphyria (Cutaneous) Testing Algorithm in Special Instructions.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

FECH Gene, Full Gene Analysis

Aliases
Lists additional common names for a test, as an aid in searching

EPP (Erythropoietic Protoporphyria)

Erythropoietic Protoporphyria (EPP)

Ferrochelatase Deficiency

Protoporphyria

FECHS

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Porphyria (Cutaneous) Testing Algorithm in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Varies

Shipping Instructions

Specimen preferred to arrive within 96 hours of draw.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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

 

Submit only 1 of the following specimens:

 

Preferred:

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.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Acceptable:

Specimen Type: Blood spot

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

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Ahlstrom 226 filter paper, or Blood Spot Collection Card (T493)

Specimen Volume: 2 to 5 Blood spots on collection card (Whatman Protein Saver 903 Paper; Ahlstrom 226 filter paper; or Blood Spot Collection Card, T493)

Collection Instructions:

1. An alternative blood collection option for a patient >1 year of age is finger stick.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 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. For collection instructions, see Blood Spot Collection Instructions in Special Instructions.

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

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL

Blood Spots: 5 punches-3 mm diameter

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

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

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirmation of a diagnosis of erythropoietic protoporphyria (EPP) following positive biochemical genetic test results obtained through PEE / Porphyrins Evaluation, Whole Blood

 

Carrier testing for individuals with a family history of EPP in the absence of known mutations in the family

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Porphyria (Cutaneous) Testing Algorithm in Special Instructions.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism whose clinical manifestations include painful photodermatosis without blisters and liver disease. The disorder results from decreased activity of the enzyme ferrochelatase (FECH). FECH is the last of 8 enzymes acting sequentially in the heme biosynthetic pathway and is encoded by the FECH gene located on chromosome 18.

 

The skin symptoms in EPP include immediate painful photosensitivity, usually beginning in early infancy upon sun exposure. Repeated photosensitivity episodes result in skin thickening and areas of hyperkeratosis. This is typically noted on areas where sun exposure is most common, such as the dorsa of the hands and on the face. A small number of patients with EPP develop liver complications. Hepatic disease in EPP may include cholelithiasis and chronic liver disease progressing to rapid acute liver failure.

 

Biochemically, EPP is characterized by elevated protoporphyrin levels in red blood cells, which fluorescence under Wood's light due to the accumulation of free protoporphyrin IX. Protoporphyrin elevations may also be found in plasma and stool, but not in all patients. Urine protoporphyrin levels are usually normal unless there is liver involvement. Studies have also suggested that a reduction in activity of ferrochelatase to <50% of normal levels can induce clinical manifestations. The gold standard test for the diagnosis of EPP is biochemical analysis (PEE / Porphyrins Evaluation, Whole Blood), interpreted in the context of clinical features.

 

In most patients with EPP, a pathogenic FECH mutation that reduces enzyme activity by 50% can be identified on only 1 allele. Clinical expression of EPP typically requires a hypomorphic (low expression) FECH allele (IVS3-48T->C) in trans (on a different chromosome) with the mutation. IVS3-48T->C is a variant of the FECH gene associated with reduced gene expression. This variant is found in approximately 10% of the general Caucasian population. Autosomal recessive inheritance (2 pathogenic mutations in trans) is infrequent, accounting for <4% of EPP cases. In contrast to patients with 1 pathogenic mutation and the low-expression allele, missense mutations are far more common than null mutations.

 

It is uncertain whether protoporphyric liver failure is more common among individuals with a single null (splicing defect, nonsense, or frameshift) mutation than those with 2 pathogenic mutations as some literature has suggested. In any case, it is certain that all EPP patients should be monitored for hepatic disease and actively manage their photosensitivity.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

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

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A small percentage of individuals who are carriers or have a diagnosis of erythropoietic protoporphyria (EPP) disease may have mutations that are not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation(s), therefore, does not eliminate the possibility of positive carrier status or the diagnosis of EPP disease. For carrier testing, it is important to first document the presence of a ferrochelatase (FECH) gene mutation in an affected family member.

 

This test does not exclude the presence of mutations within other genes, such as ALAS2 (aminolevulinate, delta-, synthase 2), that are associated with EPP, X-linked or otherwise.

 

In some cases, DNA alterations of undetermined significance may be identified.

 

Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Lecha M, Puy H, Deybach JC: Erythropoietic protoporphyria. Orphanet J Rare Dis 2009;4:19

3. Schneider-Yin X, Gouya L, Meier-Weinand A, et al: New insights into the pathogenesis of erythropoietic protoporphyria and their impact on patient care. Eur J Pediatr 2000;159:719-725

4. Rufenacht UB, Gouya L, Schneider-Yin X, et al: Systematic analysis of molecular defects in the ferrochelatase gene from patients with erythropoietic protoporphyria. Am J Hum Genet 1998;62:1341-1352

5. Whatley SD, Mason NG, Holme SA, et al: Molecular epidemiology of erythropoietic protoporphyria in the U.K.. Br J Dermatol 2010;162:642-646

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Bidirectional sequence analysis is performed to test for the presence of a mutation in all coding regions and intron/exon boundaries of the ferrochelatase (FECH) gene.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

14 to 20 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81479-Unlisted molecular pathology procedure

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports