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Test Name:
Hemochromatosis Mutation Detection (S65C, H63D, and C282Y), Hereditary
- SBMF No:
36126 - Performance Lab Name:
Flow Cytometry/Molecular Pathology - Test Mnemonic:
H HEM PCR - ABN:
Required – Not FDA-Approved - CPT Code:
83890; 83896x4; 83900; 83912 - LOINC Code:
34519-9 - Also Known As:
HFE Gene Analysis - Also See:
30055 Ferritin
29100 Iron and Iron Binding Capacity, Serum
42056 Iron, Liver Tissue - Spec Type:
Whole blood - Spec Container:
Lavender top (EDTA) or Pale Yellow top (ACD-A or B) tube - Pref Vol:
5.0 mL - Min Vol:
1.0 mL - Fasting:
No - Spec Collect:
Routine venipuncture - Spec Process:
Gently invert tube to mix blood with the anticoagulant
Do not centrifuge
Do not remove plasma from cells
Forward entire tube of unprocessed whole blood to the laboratory - Spec Store Transport:
Refrigerated - Spec Stability:
1 week refrigerated (2-8°C) - Spec Reject:
Frozen or severely hemolyzed specimen - Spec Remarks:
Traditionally, a fasting transferrin-iron saturation of ≥ 60% for men and ≥ 50% for women, on at least 2 occasions, without other known causes, has been considered suggestive of HFE-HHC. - Methodology:
Real-Time Polymerase Chain Reaction (RT-PCR) - Use:
Mutation analysis can be used to confirm the diagnosis of HFE-associated hereditary hemochromatosis (HFE-HHC) when screening test results (serum transferrin-iron saturation) are elevated. - Clinical Significance:
Hereditary Hemochromatosis (HH) is a classical autosomal recessive trait most commonly found in those of Northern European background particularly of Nordic or Celtic origin. The disease is linked to two single-nucleotide polymorphisms (SNP’s) in the HFE gene. Being the most common autosomal recessive disease in the Caucasian population it occurs approximately in 1 in 200 to 400 with 1 in 8 to 10 being carriers. Located in the HLA locus of chromosome 6, two point mutations are considered to be responsible for the majority of the Hereditary Hemochromatosis cases. They are Cys282Tyr (C282Y) contained in exon 4 and His63Asp (H63D) in exon 2.
The Cys282Tyr mutation is a cysteine to tyrosine substitution at position 282 of the HFE protein (caused by a G to A transition at nucleotide position 845.) This prevents the interaction of the HFE protein with Beta-2 microglobulin leading to an inability to bind the transferrin receptor. The His63Asp mutation is a histidine to aspartic acid substitution at position 63. It is the result of a C to G transversion at position 187. The Ser65Cys (S65C) mutation is a result the result of a alanine to threonine substitution at nucleotide position 193. It is a mild mutation accounting for 1-4% of the carrier rate.
In Hereditary Hemochromatosis, nonspecific clinical symptoms, long presympotmatic phase, and relative underawareness with in the health care community contribute to the many misdiagnosed or underdiagnosed cases. Approximately 12-15% of the white population are carriers for one of the mutant HH genes and can be associated with a mild to moderate iron overload, but more importantly also carry a 3-4% risk of producing a homozygous child. Hemochromatosis causes excess iron absorption that leads to iron accumulation in tissue and organs leading to subsequent organ dysfunction and failure. The disease can also cause other serious illness like cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotrophic hypogonadism.
- Reference Range:
Negative for C282Y, H63D, and S65C mutations - Day Run:
Thu - Time Run:
12:00 pm - Time Reported:
24 hours - Test Type:
GENETIC
