|
|
| (36 intermediate revisions by 7 users not shown) |
| Line 1: |
Line 1: |
| __NOTOC__ | | __NOTOC__ |
| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
| |
|
| |
| {{Hemochromatosis}} | | {{Hemochromatosis}} |
| {{CMG}} | | {{CMG}}; {{AE}}{{SKA}} |
|
| |
|
| ==Overview==
| | {{SK}} Haemochromatosis, Hereditary Hemochromatosis |
| '''Hemochromatosis''', also spelled '''haemochromatosis''', is a [[hereditary disease]] characterized by improper dietary [[iron]] [[metabolism]] (making it an [[iron overload disorder]]), which causes the accumulation of [[iron]] in a number of body tissues.<ref>[http://www.cdc.gov/ncbddd/hemochromatosis/ Iron Overload and Hemochromatosis] Centers for Disease Control and Prevention</ref> Iron accumulation can eventually cause end organ damage, most importantly in the [[pancreas]] manifesting as [[diabetes]], and [[liver]] failure. It is estimated that roughly one in every 300-400 people are affected by the disease, primarily of Northern European and Anglo-English descent.
| |
|
| |
|
| [[Hereditary hemochromatosis]] is the concept that known, measurable genetic mutations can be passed from generation to generation and cause iron accumulation, though not all clinical iron overload is associated with known hereditary markers, and not all hereditary markers cause significant iron overload. Semantically, therefore, the condition of a hereditary mutation in the iron metabolism genetic apparatus is not synonymous with clinical iron overload, though the term “hemochromatosis” is used to encompass both these concepts. | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
| | {{Infobox_Disease | |
| | Name = {{PAGENAME}} | |
| | Image = | |
| | Caption = | |
| | DiseasesDB = 5490 | |
| | ICD10 = {{ICD10|E|83|1|e|70}}| |
| | ICD9 = {{ICD9|275.0}}| |
| | ICDO = | |
| | OMIM = 235200| |
| | MeshName = Hemochromatosis | |
| | MeshNumber = | |
| | }} |
|
| |
|
| == History == | | ==[[Hemochromatosis overview|Overview]]== |
|
| |
|
| The disease was first described in 1865 by [[Armand Trousseau]] in an article on [[diabetes mellitus|diabetes]] in patients with changing skin color.<ref> name=Trousseau_1865>{{cite journal | author = Trousseau A| title = Glycosurie, diabète sucré | journal = Clinique médicale de l'Hôtel-Dieu de Paris | year = 1865 | volume = 2| pages = 663–98 | url= }}</ref> Trousseau did not connect the [[diabetes]] with [[iron]] accumulation; instead this was done by [[Friedrich Daniel von Recklinghausen]] in 1890.<ref>{{cite journal | author = von Recklinghausen FD | title = Hämochromatose | journal = Tageblatt der Naturforschenden Versammlung 1889 | year = 1890 | pages = 324 | url= }}</ref><ref>[http://www.whonamedit.com/doctor.cfm/1174.html Biography of Daniel von Recklinghausen]</ref>
| | ==[[Hemochromatosis historical perspective|Historical Perspective]]== |
|
| |
|
| == Epidemiology == | | ==[[Hemochromatosis classification|Classification]]== |
|
| |
|
| Hemochromatosis is one of the most common inheritable genetic defects, especially in people of northern European extraction, with about 1 in 10 people carrying a mutation in one of the [[genes]] regulating [[iron]] [[metabolism]]. The [[prevalence]] of hereditary mutations in iron metabolism [[genes]] varies in different populations. In Northern Europeans it is of the order of one in 400 persons. A study of 3,011 unrelated white Australians found that 14% were [[heterozygous]] carriers of an [[HFE]] mutation, 0.5% were [[homozygous]] for an [[HFE]] mutation, and only 0.25% of the entire population had a clinically relevant [[iron]] overload [[syndrome]]. This means that most patients who are [[homozygous]] for [[HFE]] [[mutations]] will not manifest clinically relevant hemochromatosis (see genetics below).<ref name=Olynwk_1999>{{cite journal |author=Olynyk J, Cullen D, Aquilia S, Rossi E, Summerville L, Powell L |title=A population-based study of the clinical expression of the hemochromatosis gene |journal=N Engl J Med |volume=341 |issue=10 |pages=718-24 |year=1999 |pmid=10471457}}</ref> Other populations probably have a lower prevalence of both the genetic mutation and the clinical disease. It is presumed, through [[Genetics|genetic]] studies, that the original haemochromatosis [[mutation]] arose in a single person, possibly of Celtic ethnicity, who lived 60-70 generations ago. Around that time, when [[nutrition]] was less balanced than today, the presence of a [[mutant allele]] may have provided a [[natural selection]] reproductive advantage in maintaining sufficient [[iron]] levels in the blood. With our current balanced diets, this 'extra help' is unnecessary and indeed harmful.
| | ==[[Hemochromatosis pathophysiology|Pathophysiology]]== |
|
| |
|
| == Genetics== | | ==[[Hemochromatosis causes|Causes]]== |
|
| |
|
| The regulation of how much iron enters the body from food is complex, and each year brings new discoveries about the numerous factors working in harmony to bring about balance in the metabolism of [[iron]] in [[humans]]
| | ==[[Hemochromatosis differential diagnosis|Differentiating Hemochromatosis from other Diseases]]== |
|
| |
|
| One of the best-characterized genes that regulates the amount of [[iron]] absorbed from food is called [[HFE]]. The [[HFE]] gene has two common mutations, C282Y and H63D.<ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=3 Hemochromatosis-Causes] Mayo Foundation for Medical Education and Research (MFMER) Retrieved March 12, 2007</ref>
| | ==[[Hemochromatosis epidemiology and demographics|Epidemiology and Demographics]]== |
|
| |
|
| Inheriting just one of the C282Y mutations ([[heterozygous]]) makes a person a carrier who can pass this mutation onward. Carriers of one [[HFE]] mutation ordinarily do not manifest with clinically relevant iron accumulation at all.
| | ==[[Hemochromatosis risk factors|Risk Factors]]== |
|
| |
|
| <gallery>
| | ==[[Hemochromatosis screening|Screening]]== |
| Image:Autorecessive.jpg|Haemochromatosis types 1-3 are inherited in an [[Recessive gene|autosomal recessive]] fashion.
| |
| Image:Autodominant2.jpg|Haemochromatosis type 4 is inherited in an [[autosomal dominant]] fashion.
| |
| </gallery>
| |
|
| |
|
| In the United States, most people with clinically measureable haemochromatosis (i.e., iron overload with or without end organ damage) have inherited two copies of C282Y — one from each parent — and are therefore [[homozygous]] for the trait. [[Mutation]]s of the ''HFE'' [[gene]] account for 90% of the cases of clinical iron overload. This gene is closely [[genetic linkage|linked]] to the [[Human leukocyte antigen|HLA-A3]] [[Locus (genetics)|locus]]. [[Homozygosity]] for the C282Y [[mutation]] is the most prevalent condition resulting in clinical iron accumulation, although [[heterozygosity]] for C282Y/H63D mutations, so-called compound heterozygotes, is also known to cause clinical iron overload. So, both [[homozygotes]] for C282Y and compound heterozygotes for C282Y/H63D are known to have clinical iron overload and hemochromatosis.
| | ==[[Hemochromatosis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
|
| |
|
| Most people with two copies of C282Y or one copy each of C282Y/H63D do not manifest clinical hemochromatosis, a phenomenon known as low [[Penetrance|incomplete penetration]]. <ref name=Olynwk_1999>{{cite journal |author=Olynyk J, Cullen D, Aquilia S, Rossi E, Summerville L, Powell L |title=A population-based study of the clinical expression of the hemochromatosis gene |journal=N Engl J Med |volume=341 |issue=10 |pages=718-24 |year=1999 |pmid=10471457}}</ref> Penetration differs between different populations.
| | ==Diagnosis== |
| | [[Hemochromatosis diagnostic study of choice|Diagnostic Study of Choice]] | [[Hemochromatosis history and symptoms|History and Symptoms]] | [[Hemochromatosis physical examination|Physical Examination]] | [[Hemochromatosis laboratory findings|Laboratory Findings]] | [[Hemochromatosis electrocardiogram|Electrocardiogram]] | [[Hemochromatosis x ray|X Ray]] | [[Hemochromatosis CT|CT]] | [[Hemochromatosis MRI|MRI]] | [[Hemochromatosis echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Hemochromatosis other imaging findings|Other Imaging Findings]] | [[Hemochromatosis other diagnostic studies|Other Diagnostic Studies]] |
|
| |
|
| Other genes whose mutations have been associated with iron overload include the [[autosomal dominant]] SLC11A3/ferroportin 1 gene and TfR2 (transferrin receptor 2). These mutations, and the iron overload they cause, are much rarer than ''HFE''-haemochromatosis.
| | ==Treatment== |
| | [[Hemochromatosis medical therapy|Medical Therapy]] | [[Hemochromatosis surgery|Surgery]] | [[Hemochromatosis primary prevention|Primary Prevention]] | [[Hemochromatosis secondary prevention|Secondary Prevention]] | [[Hemochromatosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Hemochromatosis future or investigational therapies|Future or Investigational Therapies]] |
|
| |
|
| Recently, a classification has been developed (with chromosome locations):
| | ==Case Studies== |
| | [[Hemochromatosis case study one|Case #1]] |
|
| |
|
| {| class="wikitable"
| | ==Related Chapters== |
| | '''Description''' || '''[[OMIM]]''' || '''Mutation''' || '''[[Locus (genetics)|Locus]]'''
| |
| |-
| |
| | Haemochromatosis type 1: "classical"-haemochromatosis || {{OMIM2|235200}} || [[HFE (gene)|HFE]] || 6p21.3
| |
| |-
| |
| | Haemochromatosis type 2A: juvenile haemochromatosis || {{OMIM2|602390}} || [[hemojuvelin]] ("HJV", also known as HFE2) || 1q21
| |
| |-
| |
| | Haemochromatosis type 2B: juvenile haemochromatosis || {{OMIM2|606464}} || hepcidin antimicrobial peptide (''[[HAMP]]'') or HFE2B || 19q13
| |
| |-
| |
| | Haemochromatosis type 3 || {{OMIM2|604720}} || [[transferrin receptor-2]] (TFR2 or HFE3) || 7q22
| |
| |-
| |
| | Haemochromatosis type 4 [[autosomal dominant]] haemochromatosis (all others are [[Recessive gene|recessive]]), gene mutation || {{OMIM2|604653}} || [[ferroportin]] (SLC11A3) || 2q32
| |
| |}
| |
| | |
| == Pathophysiology == | |
| [[Image:Iron metabolism svg.png|thumb|left|400px|The normal distribution of body iron stores]]
| |
| Since the regulation of [[iron]] metabolism is still poorly understood, a clear model of how hemochromatosis operates is still not available as of May, 2007. For example, [[HFE]] is only part of the story, since many patients with mutated [[HFE]] do not manifest clinical iron overload, and some patients with iron overload have a normal [[HFE]] [[genotype]].
| |
| | |
| In general, people with abnormal iron regulatory genes do not reduce their absorption of [[iron]] in response to increased [[iron]] levels in the body. Thus the [[iron]] stores of the body increase. As they increase the iron which is initially stored as [[ferritin]] is deposited in organs as [[haemosiderin]] and this is [[toxic]] to [[biological tissue|tissue]], probably at least partially by inducing [[oxidative stress]].<ref name=Shizukuda_2007>{{cite journal |author=Shizukuda Y, Bolan C, Nguyen T, Botello G, Tripodi D, Yau Y, Waclawiw M, Leitman S, Rosing D |title=Oxidative stress in asymptomatic subjects with hereditary hemochromatosis |journal=Am J Hematol |volume=82 |issue=3 |pages=249-50 |year=2007 |pmid=16955456}}</ref>.
| |
| | |
| Iron is a [[pro-oxidant]]. Thus, hemochromatosis shares common symptomology (e.g., cirrhosis and dyskinetic symptoms) with other "pro-oxidant" diseases such as [[Wilson's disease]], chronic [[manganese poisoning]], and hyperuricemic syndrome in Dalmatian dogs. The latter also experience "bronzing".
| |
| | |
| === Intestinal crypt enterocytes and iron overload===
| |
| | |
| The sensor pathway inside the [[small bowel]] [[enterocyte]] can be disrupted due to genetic errors in the [[iron]] regulatory apparatus. The [[enterocyte]] in the small bowel crypt must somehow sense the amount of circulating [[iron]]. Depending on this information, the [[enterocyte cell]] can regulate the quantity of [[iron]] [[Receptor (biochemistry)|receptors]] and channel proteins. If there is little [[iron]], the [[enterocyte cell]] will express many of these proteins. If there is a lot, the cell will turn off the expression of iron transporters.
| |
| | |
| In haemochromatosis, the [[enterocyte]] is somehow constantly fooled into thinking there is [[iron]] depletion. As a consequence, it overexpresses the necessary channel proteins, this leading to a massive, and unnecessary iron absorption. Details of how this process exactly works in health and disease are still being discovered as of May, 2007.
| |
| | |
| These iron transport proteins are named [[DMT-1]] (divalent metal transporter), for the luminal side of the cell, and [[ferroportin]], the only known cellular iron exporter, for the basal side of the cell.
| |
| | |
| ===Hepcidin-ferroportin axis and iron overload===
| |
| | |
| Recently, a new unifying theory for the pathogenesis of hereditary hemochromatosis has been proposed that focuses on the [[hepcidin]]-ferroportin regulatory axis. Inappropriately low levels of [[hepcidin]], the iron regulatory hormone, can account for the clinical [[phenotype]] of iron overload. In this theory, low levels of circulating [[hepcidin]] result in higher levels of [[ferroportin]] expression in [[intestinal]] [[enterocytes]] and reticuloendothelial macrophages. As a result, this causes iron accumulation. [[HFE]], [[hemojuvelin]], BMP's and TFR2 are implicated in regulating [[hepcidin]] expression.
| |
| | |
| ==End-organ damage==
| |
| Iron is stored in the liver, the pancreas and the heart. Long term effects of haemochromatosis on these organs can be very serious, even fatal when untreated.<ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=6 Haemochromatosis Complications]</ref>
| |
| '''[[Cirrhosis]]''': Permanent scarring of the [[liver]]. Along with other maladies like long-term alcoholism, haemochromatosis may have an adverse effect on the liver. The liver is a primary storage area for iron and will naturally accumulate excess iron. Over time the liver is likely to be damaged by iron overload. Cirrhosis itself may lead to additional and more serious complications, including bleeding from dilated veins in the [[esophagus]] and [[stomach]] ([[varices]]) and severe fluid retention in the [[abdomen]] ([[ascites]]). Toxins may accumulate in the blood and eventually affect mental functioning. This can lead to confusion or even [[coma]] (hepatic [[encephalopathy]]).
| |
| | |
| '''[[Liver]] [[cancer]]''': Cirrhosis and haemochromatosis together will increase the risk of liver cancer. (Nearly one-third of people with haemochromatosis and cirrhosis eventually develop liver cancer.)
| |
| | |
| '''[[Diabetes]]''': The [[pancreas]] which also stores iron is very important in the body’s mechanisms for sugar [[metabolism]]. Diabetes affects the way the body uses blood sugar ([[glucose]]). Diabetes is in turn the leading cause of new blindness in adults and may be involved in [[kidney failure]] and [[cardiovascular disease]].
| |
| | |
| '''[[Congestive heart failure]]''': If excess iron in the heart interferes with the its ability to circulate enough blood, a number of problems can occur including death. The condition may be reversible when haemochromatosis is treated and excess iron stores reduced.
| |
| | |
| '''[[Heart]] [[arrhythmias]]''': Arrhythmia or abnormal heart rhythms can cause heart palpitations, [[chest pain]] and light-headedness and are occasionally life threatening. This condition can often be reversed with treatment for haemochromatosis.
| |
| | |
| '''Pigment changes''': Deposits of iron in skin cells can turn skin a bronze or gray color.
| |
| | |
| == Diagnosis ==
| |
| | |
| Haemochromatosis can be difficult to diagnose in the early stages. Early signs may mimic other diseases. Stiff joints, diabetes, and fatigue, for example, are common in haemochromatosis and other maladies.<ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=5 Screening and Diagnosis]</ref>
| |
| | |
| === Signs and symptoms ===
| |
| | |
| Haemochromatosis is notoriously protean, ''i.e.'', it presents with symptoms that are often initially attributed to other diseases. It is also true that most people with hereditary hemochromatosis genetics never actually show signs or suffer symptoms of clinical iron overload(''i.e.,'' is clinically silent).<ref>[http://digestive.niddk.nih.gov/ddiseases/pubs/hemochromatosis/index.htm Hemochromatosis-Diagnosis] National Digestive Diseases Information Clearinghouse, National Institutes of Health, U.S. Department of Health and Human Services</ref>
| |
| Symptoms may include:<ref>[http://www.cdc.gov/ncbddd/hemochromatosis/ Iron Overload and Hemochromatosis] Centers for Disease Control and Prevention</ref><ref>[http://digestive.niddk.nih.gov/ddiseases/pubs/hemochromatosis/index.htm Hemochromatosis] National Digestive Diseases Information Clearinghouse, National Institutes of Health, U.S. Department of Health and Human Services</ref><ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=2 Hemochromatosis-Signs and Symptoms] Mayo Foundation for Medical Education and Research (MFMER)</ref>
| |
| | |
| * [[Malaise]]
| |
| * [[Liver cirrhosis]] (with an increased risk of [[hepatocellular carcinoma]], affecting up to a third of all [[homozygote]]s) - this is often preceded by a period of a painfully [[hepatomegaly|enlarged liver]].
| |
| * [[Insulin resistance]] (often patients have already been diagnosed with [[diabetes mellitus]] type 2) due to [[pancreatic]] damage from [[iron]] precipitation
| |
| * [[Erectile dysfunction]] and [[hypogonadism]]
| |
| * Decreased [[libido]]
| |
| * Congestive [[heart failure]], [[arrhythmia]]s or [[pericarditis]]
| |
| * [[Arthritis]] of the hands (especially the [[MCP joint|MCP]] and [[PIP joint]]s), [[knee joint|knee]] and [[shoulder joint|shoulder]] [[joint]]s
| |
| * [[Deafness]]<ref name=Jones_1983>{{cite journal |author=Jones H, Hedley-Whyte E |title=Idiopathic hemochromatosis (IHC): dementia and ataxia as presenting signs |journal=Neurology |volume=33 |issue=11 |pages=1479-83 |year=1983 |pmid=6685241}}</ref>
| |
| *[[Dyskinesia]]s, including [[Parkinsonian]] symptoms<ref name=Costello_2004>{{cite journal |author=Costello D, Walsh S, Harrington H, Walsh C |title=Concurrent hereditary haemochromatosis and idiopathic Parkinson's disease: a case report series |journal=J Neurol Neurosurg Psychiatry |volume=75 |issue=4 |pages=631-3 |year=2004 |pmid=15026513}}</ref><ref name=Jones_1983 /><ref name=Nielsen_1995>{{cite journal |author=Nielsen J, Jensen L, Krabbe K |title=Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome |journal=J Neurol Neurosurg Psychiatry |volume=59 |issue=3 |pages=318-21 |year=1995 |pmid=7673967}}</ref>
| |
| * Dysfunction of certain [[endocrine organs]]:
| |
| ** [[Pancreas|Pancreatic gland]], as above, manifesting as [[diabetes]]
| |
| ** [[Adrenal gland]] (leading to [[adrenal insufficiency]])
| |
| ** [[Parathyroid gland]] (leading to [[hypocalcaemia]])
| |
| ** [[Pituitary gland]]
| |
| ** [[Testes]] or [[ovary]] (leading to [[hypogonadism]])
| |
| * A darkish color 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 disease]]s caused by siderophilic microoganisms:
| |
| ** ''[[Vibrio vulnificus]]'' infections from eating seafood
| |
| ** ''[[Listeria monocytogenes]]''
| |
| ** ''[[Yersinia enterocolica]]''
| |
| ** ''[[Salmonella enteritidis]]'' (serotype Typhymurium)
| |
| ** ''[[Klebsiella pneumoniae]]''
| |
| ** ''[[E. coli|Escherichia coli]]''
| |
| ** ''[[Rhizopus arrhizus]]''
| |
| ** ''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]]). Cases of [[iron]] overload have been found in young children as well.
| |
| | |
| === 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 characteristic findings on unenhanced [[Computed axial tomography|CT]] and a decreased signal intensity at [[Magnetic resonance imaging|MR imaging]]. Haemochromatosis [[arthropathy]] includes degenerative [[osteoarthritis]] and [[Pseudogout|chondrocalcinosis]]. The distribution of the [[arthropathy]] is distinctive, but not unique, frequently affecting the second and third metacarpophalangeal joints of the hand. The [[arthropathy]] can therefore be an early clue as to the diagnosis of hemochromatosis.
| |
| [[MRI]] algorithms are available at research institutions to quantify the amount of iron present in the [[liver]], therefore reducing the necessity of a [[liver biopsy]] (see below) to measure the [[liver]] [[iron]] content. As of May, 2007, this technology was only available at a few sites in the USA, but documented reports of [[radiographic]] measurements of [[liver]] iron content were becoming more common. <ref name="pmid17018390">{{cite journal |author=Tanner MA, He T, Westwood MA, Firmin DN, Pennell DJ |title=Multi-center validation of the transferability of the magnetic resonance T2* technique for the quantification of tissue iron |journal=Haematologica |volume=91 |issue=10 |pages=1388-91 |year=2006 |pmid=17018390 |doi=}}</ref>
| |
| === Chemistry ===
| |
| '''Serum transferrin saturation'''- A first step is the measurement of [[transferrin]] saturation, the protein which chemically binds to iron and carries it through the blood to the [[liver]], [[spleen]] and [[bone marrow]].<ref>[http://sickle.bwh.harvard.edu/iron_transport.html Transferrin and Iron Transport Physiology]</ref> Measuring transferrin provides a measurement of iron in the blood. Saturation values of 45% are probably a good cutoff to determine whether a patient is a candidate for further testing. <ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=5 Screening and Diagnosis]</ref> The [[transferrin saturation]] is usually expressed as a percentage, and is calculated as the [[total serum iron]] level divided by the serum iron transferrin level times 100.
| |
| '''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.<ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=5 Screening and Diagnosis]</ref><ref>[http://www.nlm.nih.gov/medlineplus/ency/article/003490.htm Ferritin Test] Measuring iron in the body</ref>
| |
| Other blood tests routinely performed: [[blood count]], [[renal function]], [[liver enzyme]]s, [[electrolyte]]s, [[glucose]] (and/or an [[oral glucose tolerance test]] (OGTT)).
| |
| | |
| ===Functional testing===
| |
| | |
| Based on the history, the [[physician|doctor]] might consider specific tests to monitor organ dysfunction, such as an [[echocardiogram]] for [[heart failure]], or blood glucose monitoring for patients with hemochromatosis [[diabetes]].
| |
| | |
| === Histopathology ===
| |
| | |
| '''Liver biopsy''' - Liver biopsies involve taking a sample of tissue from the liver, using a thin needle. The amount of iron in the sample is then quantified and compared to normal, and evidence of liver damage, especially [[cirrhosis]], measured microscopically. Formerly, this was the only way to confirm a diagnosis of hemochromatosis but measures of transferrin and ferritin along with a history are considered adequate 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]] is still necessary to quantify the amount of accumulated iron.<ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=5 Screening and diagnosis] Mayo Foundation for Medical Education and Research (MFMER) Retrieved 18 March, 2007</ref>
| |
| | |
| === 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, are not 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:<ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=5 Screening and Diagnosis] Mayo Foundation for Medical Education and Research (MFMER). Retrieved 18 March, 2007</ref><ref>[http://www.annals.org/cgi/content/full/143/7/I-46 Screening for Hereditary Hemochromatosis: Recommendations from the American College of Physicians Annals of Internal Medicine (2005) 4 October, Volume 143 Issue 7. (Page I-46). American College of Physicians. Retrieved 18 March, 2007</ref>
| |
| *Joint disease
| |
| *Severe fatigue
| |
| *Heart disease
| |
| *Elevated liver enzymes
| |
| *Impotence
| |
| *Diabetes
| |
| Routine [[screening]] of the general population for hereditary hemochromatosis, that is, by genetic testing, has been evaluated by the US Preventive Services Task Force (USPSTF), among other groups. The USPSTF recommended against doing genetic testing to screen the general population for hereditary hemochromatosis because the likelihood of diagnosing clinically relevant, iron accumulating hereditary hemochromatosis in a treatable patient population approaches less than 1 in 1000 unselected patients. Also, there is no evidence that doing [[phlebotomy]] to treat asymptomatic, non-iron overloaded carriers of [[HFE]] mutations has any clinical benefit. Also, genetic carriers of the disease may never manifest the symptoms of the disease, so that the potential harm of the attendant surveillance, privacy issues, unnecessary invasive work-up, and anxiety outweigh the potential benefits. <ref name="pmid16880462">{{cite journal |author= |title=Screening for hemochromatosis: recommendation statement |journal=Ann. Intern. Med. |volume=145 |issue=3 |pages=204-8 |year=2006 |pmid=16880462 |doi=}}</ref> <ref>[http://www.ahrq.gov/clinic/uspstf/uspshemoch.htm Screening for Hemochromatosis] U.S. Preventive Services Task Force (2006). Summary of Screening Recommendations and Supporting Documents. Retrieved 18 March, 2007</ref>
| |
| | |
| == 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 (biology)|polymorphism]] in the gene for [[ferroportin]] which predisposes some people of African descent to iron overload.<ref name=Gordeuk_2003>{{cite journal |author=Gordeuk V, Caleffi A, Corradini E, Ferrara F, Jones R, Castro O, Onyekwere O, Kittles R, Pignatti E, Montosi G, Garuti C, Gangaidzo I, Gomo Z, Moyo V, Rouault T, MacPhail P, Pietrangelo A |title=Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene |journal=Blood Cells Mol Dis |volume=31 |issue=3 |pages=299-304 |year=2003 |pmid=14636642}}</ref>
| |
| * '''[[Transfusion hemosiderosis]]''' is the accumulation of iron, mainly in the [[liver]], in patients who receive frequent [[blood transfusion]]s (such as those with [[thalassemia]]).
| |
| * '''Dyserythropoeisis''', also known as [[myelodysplastic syndrome]] 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.
| |
| | |
| == Treatment ==
| |
| Early diagnosis is important because the late effects of iron accumulation can be wholly prevented by periodic [[Venipuncture|phlebotomies]] (by venesection) comparable in volume to [[blood donation]]s.<ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=7 Hemochromatosis - Treatment]</ref> Treatment is initiated when [[ferritin]] levels reach 300 micrograms per litre (or 200 in nonpregnant [[premenopausal]] women).
| |
| | |
| Every bag of blood ml) contains 200-250 milligrams of iron. Phlebotomy (or [[bloodletting]]) is usually done at a weekly interval until [[ferritin]] levels are less than 20 nanograms per millilitre. After that, 1-4 donations per year are usually needed to maintain iron balance.
| |
| | |
| Other parts of the treatment include:
| |
| | |
| * Treatment of organ damage ([[heart failure]] with [[diuretic]]s and [[ACE inhibitor]] therapy).
| |
| * Limiting intake of alcoholic beverages, [[vitamin C]] (increases iron absorption in the gut), red meat (high in [[iron]]) and potential causes of food poisoning (shellfish, seafood).
| |
| * Increasing intake of substances that inhibit iron absorption, such as high-[[tannin]] [[tea]], [[calcium]], and foods containing [[Oxalic acid|oxalic]] and [[phytic acid]]s (these must be consumed at the same time as the iron-containing foods in order to be effective.)
| |
| | |
| == See also ==
| |
| * [[Cirrhosis]] | | * [[Cirrhosis]] |
|
| |
| == External links ==
| |
| * [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=235200 Hemachromatosis page at the National Center for Biotechnology Information]
| |
|
| |
|
| ==References== | | ==References== |
| <!-- ---------------------------------------------------------------
| | {{reflist|2}} |
| See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for a
| |
| discussion of different citation methods and how to generate
| |
| footnotes using the <ref> & </ref> tags and the {{Reflist}} template
| |
| -------------------------------------------------------------------- -->
| |
| {{Reflist|2}}
| |
| | |
|
| |
|
| {{Hematology}} | | {{Hematology}} |
|
| |
|
| [[de:Hämochromatose]]
| |
| [[es:Hemocromatosis]]
| |
| [[fr:Hémochromatose génétique]]
| |
| [[it:Emocromatosi]]
| |
| [[he:המוכרומטוזיס]]
| |
| [[nl:Hemochromatose]]
| |
| [[no:Hemokromatose]]
| |
| [[pl:Hemochromatoza]]
| |
| [[pt:Hemocromatose]]
| |
| [[fi:Hemokromatoosi]]
| |
| [[sv:Hemakromotos]]
| |
| {{WikiDoc Help Menu}}
| |
| {{WikiDoc Sources}}
| |
|
| |
| [[Category:Disease]]
| |
| [[Category:Cardiology]]
| |
| [[Category:Gastroenterology]] | | [[Category:Gastroenterology]] |
| [[Category:Genetic Disease]]
| |
| [[Category:Hematology]] | | [[Category:Hematology]] |
| [[Category:Mature chapter]]
| |
| [[Category:Hepatology]] | | [[Category:Hepatology]] |
| [[Category:Orthopedics]]
| | |
| [[Category:Endocrinology]]
| | |
| | |
| | {{WikiDoc Help Menu}} |
| | {{WikiDoc Sources}} |