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The benefits and distractions of genetic testing


The benefits and distractions of genetic testing

Knowing if you have one, two or some combination of the three mutations of HFe is of great benefit to those who understand risk. The three possible mutations are C282Y, H63D, and S65C.

The benefit of this knowledge is having the opportunity to alter one’s diet, cut back on alcohol, donate blood, and seek regular monitoring of iron levels long before iron can damage vital organs and cause disease.

The distraction comes when genetic testing is done without fully understanding what the HFe genes represent: an adult onset condition. Not all combinations will result in excessive iron accumulation or disease. Very importantly, with the exception of “iron fist” the symptoms associated with iron overload – fatigue, joint pain, and, infertility – liver and heart disease are not specific to hereditary hemochromatosis. Granted, keeping your iron levels within a healthy range is a wise decision whether you have the genes or not.

Genetics is a fascinating field and with the rise in personalized medicine, therapies, and approaches to clinical management. For now, a clinician can use the Iron Disorders Institute Physician Hemochromatosis Reference Handout which is based on inputs from iron experts such as the members of IDI’s Scientific and Medical Advisory Board and clinical researchers at the National Institutes of Health, particularly Dr. Susan Leitman and her team at the Warren G. Magnuson Clinic.

Other genetic iron disorders such as juvenile hemochromatosis can occur in children, but this condition is not HFe related. This is particularly confusing when a child is genetically tested and found to have one or two mutations of HFe. In some cases, a mother’s concern for her child can lead to mistakes. Pediatric ranges for serum ferritin are different from adult ranges. And serum ferritin is not always a reliable indicator of elevated iron, especially in children. A child, for example, can have fairly significant elevated serum ferritin due to a mild earache or infection because serum ferritin rises in response to inflammation just as it does to excess iron. If a child has a fever when iron tests are performed, the results are skewed and a mother can worry that iron levels are rising due to genetics.

A sensitized patient or physician is the first step towards an increased level of knowledge about an iron disorder. Genetic testing of abnormal iron levels, especially serum ferritin, can prompt a complete diagnosis. But then comes the challenge of therapy. As odd as it may sound, a hemochromatosis patient can experience a variety of iron disorders - including a combination of inherited conditions such as beta thalassemia.

Do we need to be genetically tested when iron levels are elevated? IDI calls for iron levels first, then genetic testing with the benefit of a physician and a genetics counselor. Whichever door you enter first remember this: genetics only reveals risk and does not (yet) determine the therapies for iron reduction.  A person’s iron levels dictate this step in clinical management. With a complete set of iron results a trained professional can address iron deficiency (with or without anemia), iron overload, iron avidity, or anemia of inflammatory response—any or all disorders of iron that may be seen in a hemochromatosis patient during the course of clinical management.

THE IRON PANEL 
*includes fasting serum iron, total iron binding capacity, serum ferritin and hemoglobin. Some doctors will include transferrin and not the transferrin-iron saturation percentage (TS%) which is a calculation of serum iron divided by TIBC X 100% and is an indirect measurement of transferrin. UIBC also may be seen on lab tests; it too provides an indirect measurement of transferrin.
Note: if you are presently using the healtheiron.com provision, the turn-around time is 5-7 business days. This has to do with the analysis of transferrin.

Other resources on genetics and iron disorders

Genetics worksheets: http://www.irondisorders.org/genetics/

The National Society of Genetic Counselors: http://www.nsgc.org/

Health-e-Iron: http://www.healtheiron.com/hereditary-hemochromatosis

Diet for hemochromatosis: http://www.irondisorders.org/diet/

Recommended reading: links are provided where full text is available

Bacon, Adams, Kowdley, Powell and Tavill. American Association for the Study of Liver Diseases (AASLD) 2011 Practice Guidelines. http://www.aasld.org/sites/default/files/guideline_documents/Hemochromatosis2011.pdf

Feldman AG, Whitington PF. Neonatal hemochromatosis. Journal of Clinical and Experimental Hepatology. 2013 (4): 313-20.

Hulihan MM1, Sayers CA, Grosse SD, Garrison C, Grant A. Iron overload: What is the role of public health? American Journal of Preventive Medicine. 2011 41(6 Suppl 4):S422-7.
https://www.ncbi.nlm.nih.gov/pubmed/22099368

Mainous AG 3rd, Knoll ME, Everett CJ, Hulihan MM, Grant AM, Garrison C, Koenig G, Sayers C, Allen KW. A national survey of hemochromatosis patients. Journal of the American Board of Family Medicine. 2012 Jul-Aug; 25(4):432-6. https://www.ncbi.nlm.nih.gov/pubmed/22773711

Sivakumar M, Powell L. Management of human factors engineering-associated hemochromatosis: A 2015 update. World Journal of Hepatology. 2016 Mar 18;8(8):395-400.
https://www.ncbi.nlm.nih.gov/pubmed/27004087

Steinberg KK, Cogswell ME, Chang JC, Caudill SP, McQuillan GM, Bowman BA, Grummer-Strawn LM, Sampson EJ, Khoury MJ, Gallagher ML. Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States. JAMA. 2001 285(17):2216-22.
https://www.ncbi.nlm.nih.gov/pubmed/?term=steinberg+prevalence+of+C282Y

Weinberg ED. Iron availability and infection. Biochimica et Biophysica Acta 2009 Jul;1790(7):600-5.

Weinberg, ED. Hazards of iron loading. Metallomics 2010 (2): 732-40.

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