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Hereditary Hemochromatosis (HFE) - 3 Mutations (8000101246)
Test Mnemonic:


Specimen Requirements:

Whole blood


Lavender (EDTA), pink (K2EDTA), blue (Na Citrate) or yellow (Acid Citrate Dextrose) color tube.

Minimum Volume:





30 days

Causes for Rejection:

Incorrect tube, Inadequate volume

Reference Range:


Turnaround Time:

3-7 days




Moleuclar Diagnostics Laboratory


Hemochromatosis, HFE, HFE Genotype, C282Y, H63D, S65C

CPT 4 Code:



Phenotype Characteristics: Hereditary hemochromatosis (HH) results from a mutated hemochromatosis (HFE, human factors engineering) protein wherein the body accumulates excess iron. Excessive iron storage can lead to increased skin pigmentation and diseases including arthritis, hypogonadism, diabetes mellitus, heart arrhythmias/failure, cirrhosis and liver carcinoma. This test establishes HH diagnosis in individuals with abnormal iron study results and identifies at-risk family members.

Mutations in the HFE gene that cause hereditary hemochromatosis also increase the risk of developing the most common form of porphyria, porphyria cutanea tarda. The C282T HFE mutation may also increase the severity of the iron overload in X-linked sideroblastic anemia when it is inherited with a mutation in the ALAS2 gene.

 Incidence: One in 300 individuals of Northern European descent; less common in other population.

Inheritance: Autosomal recessive.

 Penetrance: The most penetrant of these mutations is C282Y; C282Y homozygotes account for up to 90% of clinical cases of hereditary hemochromatosis. H63D and S65C homozygosity typically cause only mild disease or no clinical consequences.

 Mutation Tested: p.C282Y (c.845G>A), p.H63D (c.187C>G), and p.S65C (c.193A>T).

 Methodology: Mutations are detected using genomic DNA and pyrosquencing of PCR products. This test was developed and its performance characteristics were determined by UTMB Pathology Molecular Diagnostics Laboratory. It has not been cleared or approved by the U. S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory testing.

Analytic Sensitivity and Specificity: 99 percent.

 Limitations: Diagnostic errors can occur due to rare sequence variations. HFE mutations, other than those targeted, will not be detected.

Counseling and informed consent are recommended for genetic testing. Consent form is available online.



Genetics Home Reference:

When ordering tests for which Medicare or Medicaid reimbursement will be sought, physicians should only order tests that are medically necessary for the diagnosis or treatment of the patient. Components of the organ or disease panels may be ordered individually. The diagnostic information must substantiate all tests ordered and must be in the form of an ICD-10 code or its verbal equivalent.
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