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Haemochromatosis is difficult to diagnose in the early stages. Early signs may mimic other diseases. Stiff joints and fatigue for example are common in haemochromatosis and other maladies.
Imaging features
Clinically the disease may be silent, but characteristic radiological features may point to the diagnosis. The increased iron stores in the organs involved, especially in the liver and pancreas, result in an increased attenuation at unenhanced CT and a decreased signal intensity at MR imaging. Haemochromatosis arthropathy includes degenerative osteoarthritis and chondrocalcinosis. The distribution of the arthropathy is distinctive, but not unique, frequently affecting the second and third metacarpophalangeal joints of the hand.
Chemistry
Serum transferrin saturation: A first step is the measurement of transferrin, the protein which chemically binds to iron and carries it through the blood to the liver, spleen and bone marrow. Measuring transferrin provides a measurement of iron in the blood. Saturation values of 45% are too high.
Serum Ferritin: Ferritin, the protein which chemically binds to iron and stores it in the body. Measuring ferritin provides a measurement of iron in the whole body. Normal values for males are 12-300 ng/ml (nanograms per milliliter) and for female, 12-150 ng/ml. Low values indicate iron deficiency which may be attributed to a number of causes. Higher than normal also may indicate other causes including haemochromatosis.
Other blood tests routinely performed: blood count, renal function, liver enzymes, electrolytes, glucose (and/or an oral glucose tolerance test (OGTT)).
Based on the history, the doctor might consider specific tests to monitor organ dysfunction, such as an echocardiogram for heart failure.
Histopathology
Liver biopsy - Liver biopsies involve taking a sample of tissue from your liver, using a thin needle. The sample is then checked for the presence of iron as well as for evidence of liver damage (particularly cirrhosis: tissue scarring). Formerly, this was the only way to confirm a diagnosis of hemochromatosis but measures of transferrin and ferritin along with a history are considered better options in determining the presence of the malady. Risks of biopsy include bruising, bleeding and infection. Now, when a history and measures of transferrin or ferritin point to haemochromatosis, it is debatable whether a liver biopsy still needs to occur to quantify the amount of accumulated iron.
Screening
Screening specifically means looking for a disease in people who have no symptoms. Diagnosis, on the other hand refers to testing people who have symptoms of a disease. Standard diagnostic measures for haemochromatosis, serum transferrin saturation and serum ferritin tests, aren't a part of routine medical testing. Screening for hemochromatosis is recommended if the patient has a parent, child or sibling with the disease, or have any of the following signs and symptoms:
* Joint disease
* Severe fatigue
* Heart disease
* Elevated liver enzymes
* Impotence
* Diabetes
Genetic screening does not have any apparent advantages and treatment based on screening results are not demonstrably efficacious. Given that the malady is very rare in the general population, genetic carriers of the disease may never manifest the symptoms of the disease and the potential harm of the attendant surveillance, labeling, unnecessary invasive work-up, anxiety, and, potentially, unnecessary treatments outweigh the potential benefits.
Differential diagnosis
There exist other causes of excess iron accumulation, which have to be considered before Haemochromatosis is diagnosed.
* African iron overload, formerly known as Bantu siderosis, was first observed among people of African descent in Southern Africa. Originally, this was blamed on ungalvanised barrels used to store home-made beer, which led to increased oxidation and increased iron levels in the beer. Further investigation has shown that only some people drinking this sort of beer get an iron overload syndrome, and that a similar syndrome occurred in people of African descent who have had no contact with this kind of beer (e.g., African Americans). This led investigators to the discovery of a gene polymorphism in the gene for ferroportin which predisposes some people of African descent to iron overload.
* Transfusion hemosiderosis is the accumulation of iron, mainly in the liver, in patients who receive frequent blood transfusions (such as those with thalassemia).
* Dyserythropoeisis is a disorder in the production of red blood cells. This leads to increased iron recycling from the bone marrow and accumulation in the liver.
Haemochromatosis
The gene that controls the amount of iron absorbed from food is called HFE. The HFE gene has two common mutations, C282Y and H63D.
Inheriting just one of the C282Y mutations (heterozygous) makes a person a carrier who can pass this mutation onward. One mutation may lead to slightly excessive iron absorbtion but usually haemochromatosis does not develop.
In the United States, most people with haemochromatosis have inherited two copies of C282Y — one from each parent — and are homozygous for the trait. Mutations of the HFE gene account for 90% of the cases. This gene is closely linked to the HLA-A3 locus. Homozygosity for the C282Y mutation is the most important one, although the heterozygosity C282Y/H63D mutations are also associated to disease (both conditions are sufficient to reach the diagnosis). Carriers of a single copy of either gene have a very slight risk of haemochromatosis when other factors contribute, but are otherwise healthy.
Even if an individual has both copies of the abnormal gene the risk of actual clinical haemochromatosis is low (between 1—25%) due to incomplete penetrance. The variability in these estimates is probably due to different populations studied and how penetrance was defined.
Other genes that cause haemochromatosis are the autosomal dominant SLC11A3/ferroportin 1 gene and TfR2 (transferrin receptor 2). They are much rarer than HFE-haemochromatosis.
Recently, a classification has been developed (with chromosome locations):
* Haemochromatosis type 1 (Mendelian Inheritance in Man (OMIM) 235200): "classical" HFE-haemochromatosis (6p21.3).
* Haemochromatosis type 2 (Mendelian Inheritance in Man (OMIM) 602390): juvenile haemochromatosis :
o Type 2A:(Mendelian Inheritance in Man (OMIM) 602390): mutations in hemojuvelin ("HJV", also known as HFE2)
o Type 2B (Mendelian Inheritance in Man (OMIM) 606464): mutation in hepcidin antimicrobial peptide (HAMP) or HFE2B (19q13)
* Haemochromatosis type 3 (Mendelian Inheritance in Man (OMIM) 604720): transferrin receptor-2 (TFR2 or HFE3, 7q22).
* Haemochromatosis type 4 (Mendelian Inheritance in Man (OMIM) 604653): autosomal dominant haemochromatosis (all others are recessive), ferroportin (SLC11A3) gene mutation (2q32).
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The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other
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