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.
Polymerase Chain Reaction/Fluorescence Monitoring
New York DOH Approval Status
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 1 mL)
Frozen specimens in glass collection tubes.
Ambient: 72 hours; Refrigerated: 1 week; Frozen: 1 month
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.
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.
This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
Laboratory Developed Test (LDT)
This test is not recommended for asymptomatic patients under 18 years of age.
|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|
- HLA-H Gene
- Hemochromatosis (HFE) Genotype
- HFE Gene