Assessment of Haemochromatosis
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Iron storage disease or genetic haemochromatosis is a common problem in our society. The exact frequency of the disorder remains a little uncertain even though there has been the recent discovery of a common genetic mutation identified in a large proportion of patients with this condition.
In discussing the assessment of haemochromatosis we need to evaluate firstly whether the disease is indeed present and secondly evaluate the effects of the iron overload if it does exist.
Assessing for Haemochromatosis
It was hoped that the discovery of the C282Y mutation in a significant proportion of patients with genetic haemochromatosis would solve our problem when screening family members for this disease. The passage of a mere 12 months has shown us that people who have this genetic mutation may not have iron overload, that carriers of the gene rather than homozygote individuals may have iron overload and finally it has been shown that some people with classic haemochromatosis do not have the genetic abnormality at all. The most recent article in the Journal of American Medical Association has suggested that we should not use the genetic screening test at all in seeking to identify individuals who may have iron storage disease.
I believe this is a fairly extreme stand and the genetic test is obviously going to be of value in relatives of patients who have the full blown disease and who have present genes. In these families it is appropriate to seek the mutation in the sibs and children of the identified patient.
In assessing a patient coming out of the blue with the possibility of iron storage disease, I believe the following tests still need to be undertaken – iron studies, which will include serum iron, transferrin level and transferrin saturation along with serum ferritin.
Repeated papers from numerous groups have indicated that a transferrin saturation of greater than 55% is significant and should be a trigger to press further in the search of significant iron storage disease. This test is more sensitive and more specific than a high ferritin, as ferritin concentration may be elevated in a whole range of conditions, many of which have nothing to do with elevation of iron stores.
A brief list of conditions that can be associated with a high serum ferritin in the presence of normal iron studies include malignancy, renal failure, thyrotoxicosis, inflammation of any significant degree, Hepatitis and excessive alcohol intake. NASH the syndrome of non alcoholic steato Hepatitis is also commonly associated with a high serum ferritin level.
If an individual presents with a high transferrin saturation it is imperative for the clinician to determine wether this is significant, firstly by repeating the test to ensure that it was not just laboratory aberration and at the same time if ferritin has not been measured to measure serum ferritin.
If both transferrin saturation and ferritin are high it does suggest the need to diagnose genetic haemochromatosis unless the patient has advanced liver disease at which time transferrin will be low because of protein synthetic failure.
Having identified a patient with genetic haemochromatosis a liver biopsy must be considered to confirm that the liver is indeed iron loaded and to document the severity of the disease. Having undertaken these tests, treatment should be considered and family screening should be undertaken. If a classic case is shown to have the genetic mutation then family members, which should include sibs, parents and children, should be screened with that genetic test to identify who are carriers and who have the disease. If the patient does not have the classic mutation then the family members need to be studied using the standard iron studies.
In assessing children it needs to be born in mind that many of these children will not show any evidence of iron loading until their late teens or indeed their 20’s or 30’s. Normal iron studies in children do not therefore exclude the disease.
Evaluation the Extent of the Damage
Haemochromatosis can lead to multi organ damage and those organs effected include the liver, pancreas, gastrointestinal tract, skin, heart, pituitary, testes and joints.
In evaluating a patient with iron storage disease, all of these organ systems need to be evaluated clinically and if necessary by laboratory investigations or imaging techniques. A patient needs to be advised at the outset of the extent of their tissue injury and needs to be advised that even with venesection some of these conditions eg the arthritis, may progress rather than improve.
A baseline work up should include a cardiogram, blood sugar level, liver function tests and clinical examination to determine whether there is any evidence of hypogonadism. X-rays of joints are undertaken if there is any clinical history of joint pain.
Written by: Professor Robert Batey, Director Gastroenterology, JHH
Written: September 1998
Last Reviewed: 10.5.01