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Page: Signs and Symptoms
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Haemochromatosis is notoriously protean, i.e., it presents with symptoms that are often initially attributed to other diseases. It is also true that some people with the disease never actually show signs or suffer symptoms (i.e. is clinically silent).
Symptoms may include:
* Malaise
* Liver cirrhosis (with an increased risk of hepatocellular carcinoma, affecting up to a third of all homozygotes) - this is often preceded by a period of a painfully enlarged liver.
* Insulin resistance (often patients have already been diagnosed with diabetes mellitus type 2)
* Erectile dysfunction and hypogonadism
* Decreased libido
* Congestive heart failure, arrhythmias or pericarditis
* Arthritis of the hands (MCP and PIP joints), knee and shoulder joints
* Deafness[9]
* Dyskinesias, including Parkinsonian symptoms
* Dysfunction of certain endocrine organs:
o Pancreatic gland
o Adrenal gland (leading to adrenal insufficiency)
o Parathyroid gland (leading to hypocalcaemia)
o Pituitary gland
o Testes or ovary (leading to hypogonadism)
* A darkish colour to the skin (see pigmentation, hence its name Diabete bronze when it was first described by Armand Trousseau in 1865)
* An increased susceptibility to certain infectious diseases caused by:
o Vibrio vulnificus infections from eating seafood
o Listeria monocytogenes
o Yersinia enterocolica
o Salmonella enteritidis (serotype Typhymurium)
o Klebsiella pneumoniae
o Escherichia coli
o Rhizopus arrhizus
o Mucor species
Males are usually diagnosed after their forties, and women about a decade later, owing to regular iron loss by menstruation (which ceases in menopause), but cases have been found in young children as well.
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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Important notice:
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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