Genetic testing in the setting of high ferritin to exclude hemochromatosis

Dr Mark Crowther is a professor and chair of the Department of Medicine and the Leo Pharma Chair in Thromboembolism Research at McMaster University.

Does a negative genetic test (C282Y and H63D) result exclude hemochromatosis in a patient with transferrin saturation >45% and ferritin level >1000?

Mark Crowther, MD, MSc: Absolutely not. This is a very common error that people make: a patient will show up with a high ferritin and high transferrin saturation. They have the 2 genetic tests done, they are negative, and the patient is told they do not have iron overload. Iron overload is a clinical diagnosis. If you have a ferritin >1000 and a transferrin saturation >45%, you have iron overload.

A little secret that I have that I will say now to the world is that in the 25 years I have been doing hematology I have never once ordered hemochromatosis gene testing because in my opinion it is almost useless. The reason I say that is because there are more than 50 genes that are involved in iron handling. If you have access to a genetic panel where you check all 50 genes, then I think genetic testing is useful, but if you only have access to those 2 genes, then it is not a very reliable test.

If a person has, as you said, those characteristics, they need a course of phlebotomy.