Hereditary Haemochromatosis
You are currently viewing an arhived page of the N.C.M.G. website. The information presented within is no longer valid. For further information, please see the Molecular Genetics page.
Background and Standard Service Information
The Molecular Genetics Division of the NCMG does not currently have the resources to take on testing previously carried out by the National Diagnostic Centre (NDC) at University College Galway. If you were previously using the NDC service, please do not send samples for haemochromatosis testing to the NCMG. We will be working with the Department of Health and Children and the Eastern Regional Health Authority to resolve this regrettable situation. Meanwhile, we recommend that all former users of the National Diagnostic Centre testing service should send their samples to a laboratory accredited for molecular genetic testing. A useful list of laboratories can be found at www.cmgs.org. If you have any enquiries, please contact the Molecular Genetics laboratory.
Hereditary haemochromatosis (HH) is an autosomal recessive disorder of iron metabolism, with an estimated carrier frequency of up to 1 in 5 in the Irish population.
HH is associated with homozygosity of a point mutation (C282Y) within the HFE gene (previously known as HLA-H), in approximately 93% of Irish patients.
The majority of the remaining cases are compound heterozygotes for the C282Y and H63D mutations.
HH involves the progressive accumulation of excessive iron, resulting in multi-organ dysfunction if untreated.
Clinical features include elevated ferritin and transferrin saturation levels, abnormal liver function, cirrhosis, hepatomas, diabetes, cardiomyopathy, and arthritis. Treatment is by phlebotomy.
Essential referral information
In addition to supplying standard patient and referral information, the following should be clearly indicated:
- Patient’s symptoms. Results of fasting transferrin saturation and ferritin levels must be provided.
- Family history details, including names & dates of birth of index case(s), and information regarding results of genetic testing in the index case(s).
Forms to help you give us the information we need are available directly from the laboratory, or can be downloaded in either PDF or HTML format from the ‘downloads’ area to the right of the page.
Restrictions on testing
Testing for symptomatic patients is restricted to referrals where results of fasting transferrin saturation and ferritin levels are provided.
Carrier or presymptomatic testing is not offered for minors. This policy is consistent with international guidelines for genetic testing of children for autosomal recessive, late onset conditions.
Because the mutations which pre-dispose to haemochromatosis are so common in the Irish population, cousins and more distant relatives of affected individuals are not at significantly increased risk of being carriers. Therefore, carrier testing will only be carried out on first-degree relatives (parent, spouse, sibling, offspring) of confirmed cases or confirmed mutation carriers.
Tests offered
Two types of test are performed on a routine basis:
- Diagnostic tests:
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Molecular confirmation of a suggested clinical diagnosis, by genotyping for the C282Y and H63D mutations.
- Carrier & Presymptomatic testing:
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Carrier/Presymptomatic analysis is conducted on first-degree relatives (parent, spouse, sibling, offspring) of confirmed cases or confirmed mutation carriers.
It is important to have as much information as possible regarding index case(s) in a family, as a full interpretation of the results may not be possible in the absence of this.
Therefore, please include information regarding genetic testing results in the index case(s), if available.
Samples required
3-5mls of blood in an EDTA tube.
Sensitivity of tests
- Diagnostic tests:
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A C282Y homozygous genotype will be evident in approximately 93% of Irish HH patients.
The majority of remaining cases are compound heterozygotes for the C282Y and H63D mutations.
A small proportion of patients will have other genotypes.
- Carrier & Presymptomatic testing:
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Carrier status for the C282Y and H63D mutations can be determined at an accuracy of > 99%.
- In a symptomatic individual, a homozygous C282Y genotype or a C282Y/H63D compound heterozygote genotype is consistent with a diagnosis of HH. It has been suggested that H63D homozygotes also have a slight risk of iron overload.
- In an asymptomatic individual, a homozygous C282Y genotype or a C282Y/H63D compound heterozygote genotype indicates an increased risk of developing haemochromatosis.
- The absence of an HFE mutation reduces the likelihood that a patient is affected with/at increased risk of developing HH. However, a diagnosis of HH cannot be excluded, as a small proportion of HH patients do not have HFE mutations.
Interpretation
It is important to note that the exact relationship between C282Y and H63D genotype and the development of clinical disease is not fully understood, as onset and progression are likely to be influenced by age, gender, and other factors, both genetic and environmental.
Current estimates indicate that, at most, 50% of individuals who have a C282Y/C282Y genotype will develop clinical complications of haemochromatosis (Burke et al, 2000, Genetics in Medicine 2;5:271-277). Thus, interpretation of results is always dependent on clinical status, as illustrated by the following selected examples:
Target reporting times
As reporting times are constantly evolving, please contact the Molecular Genetics laboratory to receive information on anticipated reporting times for your referral.
Indicative times for routine testing are listed on the Molecular Genetics section of the website.
Please Contact Us if you have not received a report within a week of your patient being due back in clinic.
Requests for copies of reports on the day that your patient is in clinic cannot normally be accommodated.