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Hereditary Hemochromatosis DNA Mutation Analysis

Test code(s) 35079X, 36193X (NY)

This is an outdated version of this FAQ. It was effective 04/20/2012 to 05/17/2016.

The current version is available here.

Question 1. What does a “heterozygous”, “homozygous”, or “compound heterozygous”   result mean?

  • Heterozygousmeans the individual carries one copy of a mutation on one chromosome. If the mutation is associated with a recessive disease such as hereditary hemochromatosis (HH), the individual is called a carrier. Carriers are typically unaffected, that is, they show no symptoms of the disease. However, a diagnosis of HH is made clinically, based on iron studies (see Question 5). If your patient has a clinical diagnosis of HH, he/she may carry a second HFE gene mutation not tested for in our panel. Additional mutation testing may be available for your patient at another lab. Call 866-GENEINFO to discuss this case with a genetic counselor.
  • Homozygousmeans the individual carries two copies of the same mutation, one on each chromosome. If the mutation is associated with a recessive disease such as HH, the individual is typically affected, that is, he/she shows symptoms of the disease. However, a diagnosis of HH is made clinically, based on iron studies (see Question 5). A homozygous result supports a clinical diagnosis of HH.
  • Compound heterozygousmeans the individual carries one copy each of two different mutations, one on each chromosome. If the mutations are associated with a recessive disease such as HH, the individual is typically affected. However, a diagnosis of HH is made clinically, based on iron studies (see Question 5). A compound heterozygous result supports a clinical diagnosis of HH.

Question 2. What is the next step if my patient tests positive for one HH mutation?

It depends on the indication for the HH test:

  1. This DNA test has not ruled out a diagnosis of HH. If your patient has findings that are clinically consistent with HH, he/she may carry a second mutation not tested for in our panel. Additional mutation testing may be available for your patient at another lab. Call 866-GENEINFO to discuss this case with a genetic counselor.
  2. If the only indication is a positive family history of HH, consider ordering iron studies on your patient to determine if he/she has findings that are clinically consistent with a diagnosis of hemochromatosis. Please call 866-GENEINFO to discuss this case with a genetic counselor. Documentation of the specific HH mutations in the family will be necessary to determine the accuracy of the testing that was performed on your patient.

Question 3. My patient has a family history of HH and has a negative HH mutation result. Does this result guarantee that my patient is not a carrier of HH?

No, please call 866-GENEINFO to discuss this case with a genetic counselor. Documentation of the specific HH mutations in the family will be necessary to determine the accuracy of the testing that was performed on your patient.

Question 4. My patient has a clinical diagnosis of hereditary hemochromatosis (HH), but the HH mutation test performed was negative (or only one mutation was detected). What should I do next?

This DNA test has not ruled out a diagnosis of HH. If your patient has findings that are clinically consistent with HH, he/she may carry a second mutation not tested for in our panel or may have mutations in a different gene. Additional mutation testing may be available for your patient at another lab. Call 866-GENEINFO to discuss this case with a genetic counselor.

Question 5. My patient's test result indicates he/she is homozygous (or compound heterozygous) for hereditary hemochromatosis (HH) mutations. Should I start therapeutic phlebotomy?

While a homozygous (or compound heterozygous) result may indicate that your patient is affected, a diagnosis of HH is established clinically using iron studies (serum transferrin saturation and serum ferritin). If not already performed, the next step is to perform iron studies to determine whether your patient is clinically affected with HH. Therapeutic phlebotomy is indicated only if the iron studies are consistent with a diagnosis of HH. Note that iron studies may be normal in pre-menopausal women with HH, due to regular menses. See Figures 1 and 2 for diagnostic algorithms.1

Figure 1. (LFT = Liver function tests) Use of serum ferritin concentration to help direct management

Figure 2. Testing strategy to establish the diagnosis of HFE-HHC

 

Question 6. The result reported for my patient only mentions that he/she is heterozygous for the C282Y mutation. Was my patient also tested for the H63D mutation?

Yes. The assay tests for both the C282Y and the H63D mutations. So, if the result indicates that your patient is heterozygous for the H63D mutation, then he/she is negative for the C282Y mutation.

 

References

  1. HFE-associated hereditary hemochromatosis. GeneReviews. U.S. National Library of Medicine, National Institutes of Health website. http://www.ncbi.nlm.nih.gov/books/NBK1440/. Accessed November 17, 2011.
This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.

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