Test Catalog

Test Id : HFE

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Hemochromatosis HFE Gene Analysis, Blood

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Overview

Test Catalog

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

           

HFE genetic testing is NOT recommended for population screening

 

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

 

With appropriate genetic counseling, predictive testing of individuals who have a family history of HH

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

Detects the 2 common disease-causing mutations: C282Y and H63D. The S65C mutation is 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 test is not recommended for population screening.

 

This assay will not detect all of the mutations that cause hereditary hemochromatosis.

 

The S65C mutation is reported only when 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.

See Hereditary Hemochromatosis 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)-Based Assay Utilizing Agena Mass Array Platform

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

Hemochromatosis HFE Gene Analysis, B

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

C282Y

H63D

Hereditary Hemochromatosis

HHEMO

HFE Gene

HLA-H Gene

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

See Hereditary Hemochromatosis 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.

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 specimen in original tube.

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions

3. If not ordering electronically, complete, print, and send a Benign Hematology Test Request Form (T755) with the specimen.

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 by 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 Ambient (preferred)
Frozen
Refrigerated

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

           

HFE genetic testing is NOT recommended for population screening

 

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

 

With appropriate genetic counseling, predictive testing of individuals who have a family history of HH

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

Detects the 2 common disease-causing mutations: C282Y and H63D. The S65C mutation is 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.

See Hereditary Hemochromatosis Algorithm in Special Instructions.

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. The disease is characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues. Iron overload can cause hepatic cirrhosis, hepatocellular carcinoma, diabetes mellitus, arthropathy, and cardiomyopathy. Such complications can generally be prevented by phlebotomy, and patients have a normal life expectancy if treated before organ damage occurs.

                                      

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 be done to confirm the diagnosis.

 

The majority of HH patients have mutations in the HFE gene. Clinically significant iron overload also can occur in the absence of known HFE mutations, so a negative HFE test does not exclude a diagnosis of iron overload or hemochromatosis.

 

The most common mutation in the HFE gene is C282Y (exon 4, 845G->A). Homozygosity for the C282Y mutation is associated with 60% to 90% of all cases of HH. Additionally, 3% to 8% of individuals affected with HH are heterozygous for this mutation. These frequencies show variability among different populations, with the highest frequency observed in individuals of northern European ancestry. Penetrance for elevated serum iron indices among C282Y homozygotes is relatively high, but not 100%. However, the penetrance for the characteristic clinical end points (such as diabetes mellitus, hepatic cirrhosis, and cardiomyopathy) is quite low. There is no test that can predict whether a C282Y homozygote will develop clinical symptoms.

 

The H63D (exon 2, 187C->G) mutation is associated with HH, but the actual clinical effects of this mutation are uncertain. Homozygosity for H63D is insufficient to cause clinically significant iron overload in the absence of additional modifying factors. However, compound heterozygosity for C282Y/H63D has been associated with increased hepatic iron concentrations. Approximately 1% to 2% of individuals with this genotype will develop clinical evidence of iron overload. 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).

 

The clinical significance of a third HFE mutation, S65C (exon 2, 193A->T), appears to be minimal. This rare variant displays a very low penetrance. Compound heterozygosity for C282Y and S65C may confer a low risk for mild HH. Individuals who are heterozygous for S65C and either the wild-type or H63D alleles do not seem to be at an increased risk for HH. The S65C mutation is only reported when it is part of the C282Y/S65C genotype.

 

See Hereditary Hemochromatosis Algorithm in Special Instructions.

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 about hereditary hemochromatosis testing, see Hereditary Hemochromatosis Algorithm in Special Instructions.

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

This assay will not detect all of the mutations that cause hereditary hemochromatosis. Therefore, the absence of a detectable mutation 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 our interpretation of results may occur if information given is inaccurate or incomplete.

 

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.

 

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

 

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

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

1. Mura C, Raguenes O, Ferec C: HFE Mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood 1999;93(8):2502-2505

2. Beutler E, Felitti VJ, Koziol J, et al: Penetrance of 845G->A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 2002;359(9302):211-218

3. Walsh A, Dixon JL, Ramm GA, et al: The clinical relevance of compound heterozygosity for the C282Y and H63D substitutions in hemochromatosis. Clin Gastroenterol Hepatol 2006;4(11):1403-1410

4. Whitlock EP, Garlitz BA, Harris EL, et al: Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2006;145(3):209-223

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

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 (eg, C282Y, 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
HFE Hemochromatosis HFE Gene Analysis, B 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.
52899 Result Summary 50397-9
52900 Result 21694-5
52901 Interpretation 69047-9
52902 Specimen 31208-2
52903 Source 31208-2
52904 Method 85069-3
52905 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 | Create a 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