Ordering Recommendation

Confirm clinical diagnosis of hereditary hemochromatosis (HH) in an individual with biochemical findings of iron overload. Screen adult family members of individuals with known HH. Test reproductive partner of an individual with HH for carrier status. Not recommended for initial hemochromatosis testing.

Mnemonic
HFE PCR
Methodology

Polymerase Chain Reaction/Fluorescence Monitoring

Performed

Sun-Sat

Reported

2-7 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval

C282Y Negative: The patient is negative for the HFE C282Y mutation.
H63D Negative: The patient is negative for the HFE H63D mutation.
S65C Negative: The patient is negative for the HFE S65C mutation.

Interpretive Data

Background information for Hemochromatosis (HFE) 3 Mutations:
Characteristics:
Disorder of iron metabolism resulting in excessive iron storage leading to increased skin pigmentation, arthritis, hypogonadism, diabetes mellitus, heart arrhythmias/failure, cirrhosis and liver carcinoma.
Incidence: One in 300 individuals of Northern European descent; unknown in other ethnicities.
Inheritance: Autosomal recessive.
Penetrance: 5 percent of C282Y homozygotes, 1 percent of C282Y/H63D compound heterozygotes and rare H63D homozygotes develop clinical symptoms.
Cause: Two pathogenic HFE gene mutations on opposite chromosomes.
Mutations Tested: p.C282Y (c.845G>A), p.H63D (c.187C>G), and p.S65C (c.193A>T).
Clinical Sensitivity: 85 percent of hereditary hemochromatosis in Northern Europeans is caused by C282Y homozygosity and 5 percent by C282Y/H63D compound heterozygosity.
Methodology: PCR and fluorescence monitoring.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: HFE mutations, other than those targeted, will not be detected. Diagnostic errors can occur due to rare sequence variations.

Compliance Category

Laboratory Developed Test (LDT)

Note

This test is not recommended for asymptomatic patients under 18 years of age.

Hotline History
N/A
CPT Codes

81256

Components
Component Test Code* Component Chart Name LOINC
0055606 H63D Hemochromatosis Mutation 21696-0
0055608 C282Y Hemochromatosis Mutation 21695-2
0055659 Hemochromatosis Mutation Interpretation 34519-9
0055661 S65C Hemochromatosis Mutation 38380-2
2001316 HFE PCR Specimen 31208-2
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Aliases
  • HLA-H Gene
  • C282Y
  • H63D
  • Hemochromatosis (HFE) Genotype
  • HFE Gene
Hemochromatosis (HFE) 3 Mutations