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Hereditary Hemochromatosis

Inherited mutation causing iron overload, HFE genotype

Test Codes

EPIC: LAB6384, SOFT: GHHG

Department

Molecular Pathology

Instructions

Prior to genotyping, screening with serum Ferritin and Iron Studies (Iron, TIBC, Percent Saturation) is recommended.

Specimen Collection Criteria

Collect: One 10 mL whole blood in Lavender-top EDTA tube. (Minimum: 5.0 mL)

Physician Office/Draw Specimen Preparation

Do not freeze specimens. Maintain whole blood at room temperature (20-26°C or 68-78.8°F) prior to transport.

Preparation for Courier Transport

Transport: Whole blood at room temperature (20-26°C or 68-78.8°F). (Minimum: 5.0 mL whole blood)

Rejection Criteria

• Frozen specimens.
• Unlabeled tubes.
• Specimens collected in heparin (Green-top), clot tubes (Red-top), or SST tubes.
• This test will only be performed once in a lifetime for a patient.

In-Lab Processing

Do not freeze specimens. Refrigerate (2-8°C or 36-46°F) specimens that will not be tested within 72 hours.

Storage

Specimen Stability for Testing:

Whole Blood
Room Temperature (20-26°C or 68-78.8°F): 72 hours
Refrigerated (2-8°C or 36-46°F): 7 days
Frozen (-20°C/-4°F or below): Unacceptable

Specimen Storage in Department Prior to Disposal:

Refrigerated (2-8°C or 36-46°F): 7 days

Laboratory

Royal Oak Clinical Molecular Pathology Laboratory

Performed

Once per week.
Results available in 7-10 business days.

Reference Range

Negative (no mutations).

Test Methodology

Real-Time Polymerase Chan Reation (PCR) with Allelic Discrimination.

Interpretation

• Hereditary hemochromatosis (HH) is an inherited disorder of iron metabolism, with progressive accumulation of excess iron in various sites, e.g., pancreas, liver, heart, pituitary gland, skin, and joints. Clinical symptoms include: diabetes mellitus, liver cirrhosis, gonadal failure, arthritis and skin pigmentation. The progressive increase in body iron stores leads to organ damage late in life and diagnosis in middle age or elderly men and post-menopausal women. Diagnosis may be difficult due to long periods of non-specific symptoms preceding clinical presentation (weakness, fatigue, malaise, nonspecific arthritic pain). Conventional screening and diagnostic methods (transferrin saturation, serum iron and ferritin, liver biopsy) are positive only after significant iron accumulation and potential damage have occurred.
• The HH gene (on chromosome 6) has sequence homology to Class I MHC molecules and is currently designated the HFE gene. A point mutation in the gene causes a G to A transition (G845A). Carrier frequency for heterozygosity is ~10% in phenotypically normal individuals. A second mutation in HFE, (His63Asp) contributes in so-called compound heterozygotes who have both mutations. The role of the His63Asp mutation alone in HH is unclear, since this mutation alone is quite high in asymptomatic, normal individuals.
• This assay examines two mutations, Cys282Tyr and His63Asp. Patients who test homozygous negative (normal) or homozygous mutant for Cys282Tyr will be reported as such. The vast majority (83 - 100 %) of patients with HH are homozygous for Cys282Tyr (vs. <0.5% of controls). Compound heterozygotes (those positive for both mutations) are more likely to have or develop HH than those with Cys282Tyr heterozygosity alone.
• Prior to genotyping, screening with serum Ferritin and Iron Studies (Iron, TIBC, Percent Saturation) is recommended.

Clinical Utility

Detection of hereditary hemochromatosis prior to iron overload-induced damage allows early treatment by therapeutic phlebotomy. The test is recommended for patients with clinically suspected iron overload, and laboratory documented elevated ferritin, serum iron and % saturation, as well as elevated liver function tests; the test is also recommended for patients with positive family history of hereditary hemochromatosis. Once genotypic HH diagnosis is made, blood relatives and spouses should be tested to determine individual risk factors.

CPT Codes

81256

Contacts

Last Updated

4/6/2021