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23106 Hemochromatosis, HFE Gene Analysis (HFE)

Hemochromatosis, HFE Gene Analysis (HFE)
Test Code: HCHROM
Synonyms/Keywords
C282Y, H63D, Hereditary Hemochromatosis, HHEMO, HFE Gene, HLA-H Gene
Useful For
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​
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Whole blood​ EDTA Lavender Top Tube (LTT)​ Yellow Top (ACD)​  2.5 mL​
0.5 mL​
Collection Processing Instructions
1. Invert several times to mix blood.
2. Send specimen in original tube.​
 
Specimen preferred to arrive within 96 hours of draw.
 
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.
Specimen Stability Information
Specimen Type Temperature​Time
​Whole blood ​ ​ Ambient (preferred)​​96 hours
Frozen ​​96 hours
Refrigerated ​​96 hours
Rejection Criteria
All specimens will be evaluated by Mayo Clinic Laboratories for test suitability.
Interference

​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.

Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
Mayo Clinic Laboratories​ Monday through Friday
6-7 days​
Polymerase Chain Reaction (PCR)-Based Assay Utilizing Agena Mass Array Platform
Reference Lab
Test Information

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.

Reference Range Information
Interpretive Report
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​81256
Synonyms/Keywords
C282Y, H63D, Hereditary Hemochromatosis, HHEMO, HFE Gene, HLA-H Gene
Ordering Applications
Ordering Application Description
​COM ​Hereditary Hemochromatosis
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Whole blood​ EDTA Lavender Top Tube (LTT)​ Yellow Top (ACD)​  2.5 mL​
0.5 mL​
Collection Processing
1. Invert several times to mix blood.
2. Send specimen in original tube.​
 
Specimen preferred to arrive within 96 hours of draw.
 
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.
Specimen Stability Information
Specimen Type Temperature​Time
​Whole blood ​ ​ Ambient (preferred)​​96 hours
Frozen ​​96 hours
Refrigerated ​​96 hours
Rejection Criteria
All specimens will be evaluated by Mayo Clinic Laboratories for test suitability.
Interference

​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.

Useful For
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​
Reference Range Information
Interpretive Report
For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
Mayo Clinic Laboratories​ Monday through Friday
6-7 days​
Polymerase Chain Reaction (PCR)-Based Assay Utilizing Agena Mass Array Platform
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​81256
For most current information refer to the Marshfield Laboratory online reference manual.