Test Catalog

Test Id : HFET

Hereditary Hemochromatosis, HFE Variant Analysis, Varies

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

Establishing or confirming the clinical diagnosis of hereditary hemochromatosis (HH) in adults

 

Testing of individuals with increased transferrin-iron saturation in serum and serum ferritin

 

Predictive testing of individuals who have a family history of HH, in coordination with appropriate genetic counseling

 

This test is not recommended for population screening.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test detects the 2 common disease-causing variants in the HFE gene: C282Y (c.845G>A) and H63D (c.187C>G). The S65C variant will be reported only when it    is observed as part of the C282Y/S65C genotype.

Highlights

Molecular testing can be done to establish or confirm the diagnosis of hereditary hemochromatosis in individuals with clinical symptoms.

 

This assay will not detect all variants in the HFE gene that cause hereditary hemochromatosis.

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

For more information see Hereditary Hemochromatosis Algorithm

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

Droplet Digital Polymerase Chain Reaction (ddPCR)

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

Hereditary Hemochromatosis HFE Test

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

C282Y

H63D

Hereditary Hemochromatosis

HFE Gene

HFET

HHEMO

HLA-H Gene

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

For more information see Hereditary Hemochromatosis Algorithm

Specimen Type
Describes the specimen type validated for testing

Varies

Shipping Instructions

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:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 2.5 mL

Collection Instructions:

1. Invert several times to mix blood.

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

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

 

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.

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

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: Congenital Inherited Diseases Patient Information (T521)

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

0.5 mL

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

Establishing or confirming the clinical diagnosis of hereditary hemochromatosis (HH) in adults

 

Testing of individuals with increased transferrin-iron saturation in serum and serum ferritin

 

Predictive testing of individuals who have a family history of HH, in coordination with appropriate genetic counseling

 

This test is not recommended for population screening.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test detects the 2 common disease-causing variants in the HFE gene: C282Y (c.845G>A) and H63D (c.187C>G). The S65C variant will be reported only when it    is observed as part of the C282Y/S65C genotype.

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

For more information see Hereditary Hemochromatosis Algorithm

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

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism with a carrier frequency of   approximately 1 in 10 individuals of Northern European ancestry.(1) The disease is characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues (eg, liver, skin, heart, joints). Clinical symptoms of HFE hemochromatosis usually appear in men between age 40 and 60 years and after menopause in women, and they might be affected by other factors such as intake of iron and other mineral supplements, vitamin C, and alcohol consumption. Iron overload can     lead to hepatic cirrhosis, hepatocellular carcinoma, diabetes mellitus, arthropathy, and cardiomyopathy. Such complications may be prevented by phlebotomy, and patients may have a normal life expectancy when treated before organ damage occurs.(2) For individuals with clinical symptoms consistent with HH or biochemical evidence of iron overload, an HH diagnosis is typically based on the results of transferrin-iron saturation and serum ferritin concentration. Molecular testing can also be performed to confirm/establish the diagnosis.

 

The two most common variants in the HFE gene are C282Y and H63D. The majority of HH patients (approximately 85-90%) show homozygosity for the C282Y variant and compound heterozygosity for the C282Y and H63D variants.(1) Carrier status (heterozygotes) generally do not develop complications of iron overload but may have abnormal serum iron results.(1) Furthermore, clinically significant iron overload can also occur in the absence of known HFE variants. Therefore, a negative HFE test does not exclude other rare variants in the HFE gene or in other genes and, thus, does not exclude a diagnosis of iron overload or hemochromatosis.

 

The most common disease-causing variant identified in the HFE gene is C282Y (c.845G>A in exon 4). Individuals who are homozygous for a C282Y variant account for 60% to 90% of all HH cases, however clinical penetrance is incomplete.(3) Up to 50% of individuals homozygous for a C282Y develop iron overload (elevated serum iron indices), and 10% to 33% (mainly men) develop hemochromatosis-related syndromes or end-organ damage symptoms.(2) Currently there is no test that can predict whether a C282Y homozygote will develop clinical symptoms. Additionally, 3% to 8% of individuals affected with HH are heterozygous for this variant. These frequencies show variability among different populations, with the highest frequency observed in individuals of Northern European ancestry.

 

The H63D (c.187C>G in exon 2) variant is also associated with HH, however the presence of a single H63D variant is unlikely to be of clinical significance in the absence of other disease-causing variants. Additionally, homozygosity for H63D is insufficient to cause clinically significant iron overload in the absence of other modifying risk factors. Compound heterozygotes for C282Y/H63D have higher penetrance and have been associated with increased hepatic iron concentrations. Approximately 0.5% to 2% of individuals with this genotype will develop clinical evidence of iron overload.(2) While individuals with this genotype may have increased iron indices, most will not develop clinical disease without comorbid factors (steatosis, diabetes, or excess alcohol consumption).(4)

 

The clinical significance of a third HFE variant, S65C (c.193A>T in exon 2), appears to be minimal. This rare variant displays a very low penetrance and is generally not associated with iron overload. Individuals who are heterozygous for S65C with either the wild-type or H63D allele do not seem to be at an increased risk for HH. Compound heterozygosity for C282Y and S65C may confer a low risk for mild HH.(1) Therefore, the C282Y/S65C genotype is reported when observed.

 

For more information see Hereditary Hemochromatosis Algorithm

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 interpretative report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

 

For more information see Hereditary Hemochromatosis Algorithm

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

This assay only tests for the C282Y, H63D and S65C (reported as a part of the C282Y/S65C genotype) variants and will not detect all variants in the HFE gene that may be associated with hereditary hemochromatosis. Therefore, the absence of a detectable C282Y, H63D, or S65C variant does not rule out the possibility that an individual is a carrier of or affected with this disease.

 

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

 

Rare variants (ie, 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.

 

In rare cases, DNA variants of unknown significance may be identified.

 

Because of concerns of the overall penetrance of HFE variants, HFE genetic testing is not recommended for population screening.

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

1. Barton JC, Edwards CQ. HFE Hemochromatosis. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated December 6, 2018. Accessed March 14, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1440/

2. Kowdley KV, Brown KE, Ahn J, Sundaram V: ACG Clinical Guideline: Hereditary Hemochromatosis. Am J Gastroenterol. 2019 Aug;114(8):1202-1218

3. Porto G, Brissot P, Swinkels DW, Zoller H, et al: EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH). Eur J Hum Genet. 2016 Apr;24(4):479-495

4. Hollerer I, Bachmann A, Muckenthaler MU: Pathophysiological consequences and benefits of HFE mutations: 20 years of research. Haematologica. 2017 May;102(5):809-817

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

Droplet digital polymerase chain reaction (ddPCR) is used to test for the following three variants in the HFE gene: C282Y, H63D, and S65C. Because of the minimal effect on iron metabolism associated with the S65C variant, it is only reported when it is found with the C282Y variant (ie, if the patient has the C282Y/S65C genotype).(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.

Monday through Friday

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.

6 to 7 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.

81256-HFE (hemochromatosis) (eg, hereditary hemochromatosis) gene analysis, common variants (C282Y and H63D)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
HFET Hereditary Hemochromatosis HFE Test 34519-9
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
614667 Result Summary 50397-9
614668 Result 82939-0
614669 Interpretation 69047-9
614670 Specimen 31208-2
614791 Source 31208-2
614792 Method 85069-3
614793 Released By 18771-6

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