This test is contraindicated for patients who have undergone an allogenic stem cell transplant (e.g., bone marrow or peripheral stem cell from a donor).
* All specimens will be evaluated at the Sanford Medical Genetics laboratory for test suitability.
Limitations:Rare variants in the HFE gene and other genetic factors associated with HH are not assessed by this assay. Additionally, rare genetic polymorphisms may interfere with variant assessment and lead to inconclusive results. Test results should be interpreted in the context of clinical findings, other laboratory data, family history, and environmental and lifestyle risk factors. If clinically warranted, additional testing should be considered. Allogenic bone marrow transplants may result in false-positive or false-negative results.
Test algorithm guidelines have been established and a Sanford customized algorithm is below (Kowdley et al, 2019).
Note: S65C is only reported when C282Y is identified in a heterozygous state due to its limited biochemical relevance. Studies have demonstrated that although some compound C282Y/S65C heterozygous individuals may present with increased serum iron and ferritin levels, they do not present with clinical manifestations of hemochromatosis nor iron-associated liver fibrosis (Holstrom, 2002; Pederson, 2009). Moreover, in 2019 American College of Gastroenterology (ACG) classified S65C as a polymorphism without clinical significance (Kowdley, 2019).