Background:
Hereditary hemochromatosis (HH) is an autosomal recessive disorder which leads to increased rates of intestinal iron absorption. This can cause severe tissue damage in the liver, pancreas, heart, pituitary, and other organs. The common clinical consequences are variable but include hepatic cirrhosis, diabetes mellitus, cardiomyopathy and arthropathy. Less severe symptoms include fatigue, weakness, arthralgias, and/or hyperpigmentation. The carrier frequency is highest (approximately 1 in 10 individuals) of Northern European ancestry, however, less common variants have been described in various populations (1-5).
Targeted testing for the two most common variants p.Cys282Tyr (p.C282Y) and p.His63Asp (p.H63D) is considered the first step in the genetic testing strategy. However, other less common variants have been described, therefore, a negative HFE test does not exclude other rare variants in the HFE gene and does not exclude a diagnosis of iron overload or hemochromatosis.
Reason for Referral:
Indicated in patients with a suspected iron overload disorder that cannot be explained by secondary factors (such as chronic transfusion or dyserythropoiesis).
Methodology:
DNA is isolated from the patient sample and analyzed for the presence of p.C282Y and p.H63D variants in HFE. A specific region of the HFE gene is amplified by PCR and analyzed using a fluorescently labeled mutation-specific probe. A fluorescent melting curve of hybridization kinetics of the sample and necessary controls are examined.
Specimen Requirements:
Blood: EDTA or ACD (Solution A or B)
Adult: 5mL
Child: 5mL
Infant: 2mL
DNA: 10ng at a minimum of 100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)
For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion. For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information.
Test Performed (Days):
Weekly
Turn Around Time:
7-10 Days
Shipment Sensitivity Requirements:
- Package and ship specimens to remain cold, but not frozen.
- Ship via overnight express, using the FedEx priority overnight label provided.
- Contact Client Services for shipping kits and instructions at (855) 535-1522.
References:
- Barton JC, Edwards CQ. HFE Hemochromatosis. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated December 6, 2018. Accessed January 3, 2023. Available at www.ncbi.nlm.nih.gov/books/NBK1440/
- Piperno A, Arosio C, Fossati L, Viganò M, Trombini P, Vergani A, Mancia G. Two novel nonsense mutations of HFE gene in five unrelated Italian patients with hemochromatosis. Gastroenterology. 2000;119:441–5.
- Le Gac G, Congiu R, Gourlaouen I, Cau M, Férec C, Melis MA. Homozygous deletion of HFE is the common cause of hemochromatosis in Sardinia. Haematologica. 2010;95:685–7.
- Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS, et al. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:328–43.
- Barton JC, Edwards CQ, Acton RT. HFE gene: structure, function, mutations, and associated iron abnormalities. Gene. 2015;574:179–92.
Additional Info: