HEMOCHROMATOSIS MUTATION DETECTION (S65C, H63D, & C282Y), HEREDITARY

Code
900.1814
Name
HEMOCHROMATOSIS MUTATION DETECTION (S65C, H63D, & C282Y), HEREDITARY
Category
None
Department
Send-Out
Start Date
Expiration Date
Synonyms
HFE
CPT Codes
83890; 83896x4; 83900; 83912
Site
SBMF
Reference Test
36126
ATLAS Test Code

Specimen Information

Type

Two (2) Lavender, EDTA Whole Blood

Volume

5.0 ml

Transport Info

Refrigerated

Fasting Required?
False
Patient Instructions

Reference Range

Methodology

Real-Time Polymerase Chain Reaction (RT-PCR)

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.

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