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Hemochromatosis

Diabetes Bronze

Hemochromatosis is the abnormal accumulation of iron in parenchymal organs and the most common form of iron overload disease. It may be inherited or acquired.


Presentation

The patients suffering from hemochromatosis have the following clinical picture.

  • The skin of these patients acquires a bronze pigmentation due to the excessive amounts of melanin and iron in the exposed parts along with the axilla, groin and genitalia.
  • The patients of hemochromatosis develop liver cirrhosis due to iron accumulation in the hepatic tissue. Cirrhosis may be the initial presenting feature in some of the patients.
  • The accumulation of iron in the endocrine pancreatic tissue may cause the failure of insulin production and lead to secondary insulin dependent diabetes mellitus. Cirrhosis and diabetes may or may not be accompanied by heart failure and neurologic abnormalities respectively.
  • The deposition of calcium pyrophosphate in the joints of these patients causes the development of arthritis along with chondrocalcinosis.
  • There may be a number of sexual disturbances in the patients suffering from hemochromatosis. These include loss of libido, atrophy of the testes and impotence.
Splenomegaly
  • Regression on SF revealed significant associations: TS; male sex; age; GGT; transfusion units (positive); and splenomegaly (negative) (p 0.0001, 0.0016, 0.0281, 0.0025, 0.0001, and 0.0096, respectively).[ncbi.nlm.nih.gov]
  • Here we report the case of a 16-year-old Chinese boy, who was admitted with hepatalgia, jaundice, hyperpigmentation, and splenomegaly to our hospital.[ncbi.nlm.nih.gov]
  • An abnormally enlarged spleen (splenomegaly) may also occur. Additional symptoms occur depending on the specific organs involved.[rarediseases.org]
  • In advanced cases of hemochromatosis there will likely be cardiac arrhythmias, congestive heart failure, testicular atrophy, jaundice, increased pigmentation, spider angiomas and splenomegaly.[themedicalbiochemistrypage.org]
Fatigue
  • Combined treatment with EPO and EA was well tolerated, and all 18 patients who suffered from fatigue prior to therapy recovered. Median ferritin values were 678.5 ng/L before treatment and 145 ng/L after treatment.[ncbi.nlm.nih.gov]
  • Symptoms greatly vary among patients and include fatigue, abdominal pain, arthralgias, impotence, decreased libido, diabetes, and heart failure.[ncbi.nlm.nih.gov]
  • Early symptoms may be nonspecific and often include joint pain, fatigue and weakness.[arthritis.org]
  • Male C282Y homozygotes with a serum ferritin level of 1000 mug per liter or more were more likely to report fatigue, use of arthritis medicine, and a history of liver disease than were men who had the wild-type gene.[ncbi.nlm.nih.gov]
Congestive Heart Failure
  • The prognosis is poor due to progressive congestive heart failure and refractory arrhythmias. Here we report a rare case of fatal cardiac hemochromatosis associated with HS.[ncbi.nlm.nih.gov]
  • heart failure Operative total joint arthroplasty indications large joint involvement Orthopaedic Manifestations Bilateral ankle arthritis hemochromatosis should be suspected when symmetrical ankle arthropathy occurs in young men Please rate topic.[orthobullets.com]
  • Hemochromatosis Pathology Cause(s) Genetic Symptoms Fatigue, malaise, cirrhosis, insulin resistance, erectile dysfunction, hypogonadism, congestive heart failure, arrythmia, pericarditis, arthritis, Mortality Rate Very high if untreated Treatments Bleeding[house.wikia.com]
  • This is called congestive heart failure. Hemochromatosis can also cause abnormal heart rhythms (arrhythmias). Reproductive problems.[mayoclinic.com]
Weight Loss
  • If you do, you may have joint pain, fatigue, general weakness, weight loss, and stomach pain. Your doctor will diagnose hemochromatosis based on your medical and family histories, a physical exam, and the results from tests and procedures.[medlineplus.gov]
  • Other symptoms of hemochromatosis include: Lack of energy Abdominal (belly) pain Loss of sex drive Loss of body hair Heart flutters Memory fog Weight loss Weakness Abnormal coloring of the skin (gray or bronze) Cleveland Clinic is a non-profit academic[my.clevelandclinic.org]
  • Common early symptoms of classic hereditary hemochromatosis include joint inflammation and pain (arthritis) especially in the small joints of the fingers, fatigue, weakness, abdominal pain, unintended weight loss, and an abnormally enlarged liver (hepatomegaly[rarediseases.org]
  • All encompassing symptoms may include: Joint pain Fatigue Abdominal pain Weakness Weight loss Loss of sex drive (libido) or impotence Lack of normal menstruation (amenorrhea) Loss of body hair Shortness of breath Arthritis Liver problems, such as cirrhosis[liversupport.com]
Family History of Arthritis
  • This information often provides helpful clues, such as a family history of arthritis or unexplained liver disease. Blood tests can determine whether the amount of iron stored in the body is too high.[healthieryou.com]
  • The health care provider will look for clues that may indicate hemochromatosis, such as a family history of arthritis or unexplained liver disease. Physical exam.[niddk.nih.gov]
Male Hypogonadism
  • A possible confounding factor in any analysis of male hypogonadism is the natural decline in testosterone that occurs with aging, a subject that has received much recent attention.[academic.oup.com]
Abdominal Pain
  • Symptoms greatly vary among patients and include fatigue, abdominal pain, arthralgias, impotence, decreased libido, diabetes, and heart failure.[ncbi.nlm.nih.gov]
  • Among organ-related symptoms, hepatomegaly is seen in more than 95% of patients and can be accompanied by signs of chronic liver disease, such as abdominal pain and cutaneous stigmata of liver disease (palmar erythema, spider angioma, or jaundice), and[emedicine.com]
  • Hypopituitarism can cause a wide variety of symptoms including fatigue, headaches and abdominal pain.[rarediseases.org]
  • Symptoms are rare, even in advanced cases, but when they occur they include joint pain, fatigue, abdominal pain and loss of sex drive.[emoryhealthcare.org]
Cardiomegaly
  • She showed marked elevation of serum ferritin levels (3,210 ng/ml), cardiomegaly on chest X-p, conduction disturbance on electrocardiography, and high intensity of the left and right ventricular walls on plain chest CT indicating myocardial iron deposition[jsum.or.jp]
Hepatomegaly
  • We retrospectively studied SF and post-screening age; sex; body mass index; transferrin saturation (TS); ALT; AST; GGT; elevated C-reactive protein; ß-thalassemia; neutrophils; lymphocytes; monocytes; platelets; metacarpophalangeal joint hypertrophy; hepatomegaly[ncbi.nlm.nih.gov]
  • Eight of the 16 homozygous subjects had clinical findings that were consistent with the presence of hereditary hemochromatosis, such as hepatomegaly, skin pigmentation, and arthritis.[ncbi.nlm.nih.gov]
  • Among organ-related symptoms, hepatomegaly is seen in more than 95% of patients and can be accompanied by signs of chronic liver disease, such as abdominal pain and cutaneous stigmata of liver disease (palmar erythema, spider angioma, or jaundice), and[emedicine.com]
  • Liver abnormalities associated with classic hereditary hemochromatosis include hepatomegaly, and scarring of the liver (cirrhosis), high blood pressure of the branches of the portal vein (portal hypertension), which is the main vein that carries blood[rarediseases.org]
Jaundice
  • Here we report the case of a 16-year-old Chinese boy, who was admitted with hepatalgia, jaundice, hyperpigmentation, and splenomegaly to our hospital.[ncbi.nlm.nih.gov]
  • Among organ-related symptoms, hepatomegaly is seen in more than 95% of patients and can be accompanied by signs of chronic liver disease, such as abdominal pain and cutaneous stigmata of liver disease (palmar erythema, spider angioma, or jaundice), and[emedicine.com]
  • The patient's last admission was necessitated by the development of symptoms and signs of hepatic failure (hepatic coma) characterized by jaundice Jaundice (or icterus) is a state of hyperbilirubinemia (increased bilirubin in the blood) in which bile[peir.path.uab.edu]
  • The disease can lead to organ failure, especially liver failure (cirrhosis), which can cause confusion, bleeding, fluid accumulation in the legs and abdomen, black or bloody stools, and jaundice.[drugs.com]
Hepatosplenomegaly
  • […] dysfunction in men (45% of patients with heretditary hemochromatosis) Amenorrhea Skin hyperpigmentation (like suntan) on both exposed and nonexposed areas; slate gray in late stages (75% of patients with hereditary hemochromatosis) Other manifestations Hepatosplenomegaly[faculty.washington.edu]
Hyperpigmentation
  • hyperpigmentation and actinic reticuloid.[emedicine.com]
  • PubMed was used to search the following terms: hemochromatosis, hereditary, hyperpigmentation, hypopigmentation, keratosis, melanin, seborrheic, siderosis.[ncbi.nlm.nih.gov]
  • Here we report the case of a 16-year-old Chinese boy, who was admitted with hepatalgia, jaundice, hyperpigmentation, and splenomegaly to our hospital.[ncbi.nlm.nih.gov]
  • […] treatment returns life expectancy to normal if patient non cirrhotic and no diabetic Presentation Symptoms classically presents with non-specific symptoms fatigue lethargy joint or muscle pain may present with systemic symptoms impotence diabetes skin hyperpigmentation[orthobullets.com]
Arthritis
  • Due to the apparent difficulty in differentiating between the two diseases, a screening profile of iron in patients with rheumatoid arthritis with atypical progression is necessary. [Indexed for MEDLINE] Free full text[ncbi.nlm.nih.gov]
  • A 72-year-old woman with rheumatoid arthritis diagnosed with secondary hemochromatosis underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography(PET)/computed tomography (CT) to search for malignancy.[ncbi.nlm.nih.gov]
  • […] extraction demographics usually presents in 4th-5th decade of life women usually present later than men due to the protective effect of iron loss during menses and pregnancy location multi-system disease hypogonadism diabetes liver cirrhosis cardiomyopathy arthritis[orthobullets.com]
  • Prevalences of Hashimoto's thyroiditis, rheumatoid arthritis, and ankylosing spondylitis were 8.1% (95% CI: [5.1, 12.5]), 1.7% [0.6, 4.6], and 0.0085 [0.0015, 0.0337], respectively. Eighteen probands (7.7%) had a FH.[ncbi.nlm.nih.gov]
  • Male C282Y homozygotes with a serum ferritin level of 1000 mug per liter or more were more likely to report fatigue, use of arthritis medicine, and a history of liver disease than were men who had the wild-type gene.[ncbi.nlm.nih.gov]
Arthralgia
  • Symptoms greatly vary among patients and include fatigue, abdominal pain, arthralgias, impotence, decreased libido, diabetes, and heart failure.[ncbi.nlm.nih.gov]
  • However, symptomatology of hereditary hemochromatosis has changed in recent years, and its full clinical expression is seen in only a minority of patients. [9] In addition, any patient admitted to the hospital with an isolated case of asthenia or with arthralgia[emedicine.com]
  • However, symptomatology of hereditary hemochromatosis has changed in recent years, and its full clinical expression is seen in only a minority of patients. [8] In addition, any patient admitted to the hospital with an isolated case of asthenia or with arthralgia[emedicine.medscape.com]
  • Clinical signs attributed to HFE-related HH include liver failure, arthralgia, chronic fatigue, diabetes mellitus and congestive heart failure. organ failure can be prevented by phlebotomies starting before irreversible damage has occurred.[ncbi.nlm.nih.gov]
  • Clinical manifestations Common presenting symptoms: Fatigue, often severe (75% of patients with heretditary hemochromatosis) Arthralgias Abdominal discomfort Insulin resistance and diabetes mellitus (50% of patients with hereditary hemochromatosis) Erectile[faculty.washington.edu]
Large Joint Involvement
  • joint involvement Orthopaedic Manifestations Bilateral ankle arthritis hemochromatosis should be suspected when symmetrical ankle arthropathy occurs in young men Please rate topic.[orthobullets.com]
Decreased Libido
  • Symptoms greatly vary among patients and include fatigue, abdominal pain, arthralgias, impotence, decreased libido, diabetes, and heart failure.[ncbi.nlm.nih.gov]
  • Some affected individuals may also have loss of interest in sex (decreased libido). Additional symptoms have been associated with classic hereditary hemochromatosis. These symptoms are common to all individuals as they age.[rarediseases.org]
  • Erectile dysfunction and hypogonadism, resulting in decreased libido Congestive heart failure, abnormal heart rhythms, or pericarditis Arthritis of the hands (especially the second and third metacarpophalangeal joints), but also the knee and shoulder[en.wikipedia.org]
Lethargy
  • General symptoms comprise chronic fatigue, weakness, lethargy, and apathy.[emedicine.com]
  • Early symptoms may include lethargy and weakness, irritability, depression, joint pain, yellowish skin, and loss of body hair. Regular treatment with phlebotomy or chelation therapy is needed to reduce iron levels.[massgeneral.org]
  • […] allele is most common Prognosis produces arthritis and chondrocalcinosis in 50% of patients treatment returns life expectancy to normal if patient non cirrhotic and no diabetic Presentation Symptoms classically presents with non-specific symptoms fatigue lethargy[orthobullets.com]
  • Early symptoms include arthralgias typically at the second and third MCPs, extreme fatigue, apathy, lethargy, weight loss, loss of libido, impotence, and right upper quadrant abdominal pain.[rheumatologyadvisor.com]
Apathy
  • General symptoms comprise chronic fatigue, weakness, lethargy, and apathy.[emedicine.com]
  • Early symptoms include arthralgias typically at the second and third MCPs, extreme fatigue, apathy, lethargy, weight loss, loss of libido, impotence, and right upper quadrant abdominal pain.[rheumatologyadvisor.com]
Asthenia
  • However, symptomatology of hereditary hemochromatosis has changed in recent years, and its full clinical expression is seen in only a minority of patients. [9] In addition, any patient admitted to the hospital with an isolated case of asthenia or with[emedicine.com]
  • However, symptomatology of hereditary hemochromatosis has changed in recent years, and its full clinical expression is seen in only a minority of patients. [8] In addition, any patient admitted to the hospital with an isolated case of asthenia or with[emedicine.medscape.com]
Sexual Dysfunction
  • Patients most commonly present with nonspecific symptoms such as unexplained chronic fatigue (tiredness), weakness, joint pain or stiffness, sexual dysfunction, enlarged liver, diabetes, enlarged heart or abnormal laboratory results with high liver enzymes[ihtc.org]
  • dysfunction Early-onset arthropathy, cardiomyopathy, cardiac dysrhythmias. or sexual dysfunction Patients without clinical manifestations of HH First-degree relatives of a patient with identified HH Incidental finding of elevated serum iron markers ([clevelandclinicmeded.com]
  • If it accumulates in the pituitary gland, it can cause menstrual irregularities in women and sexual dysfunction, loss of sex drive, and erectile difficulties in men.[medbroadcast.com]
Amenorrhea
  • As a result of hormonal deficiencies affected males may experience impotence and affected women may experience loss of menstrual periods (amenorrhea) or early menopause.[rarediseases.org]
  • All encompassing symptoms may include: Joint pain Fatigue Abdominal pain Weakness Weight loss Loss of sex drive (libido) or impotence Lack of normal menstruation (amenorrhea) Loss of body hair Shortness of breath Arthritis Liver problems, such as cirrhosis[liversupport.com]
  • […] women, the average age at the time of diagnosis is about 50 years. 1 Symptoms can include: Weight loss Bronze-colored skin Body hair loss Low energy level and weakness Abdominal pain Depression and irritability Tiredness Joint pain Loss of sexual desire Amenorrhea[pamf.org]
  • […] of patients with heretditary hemochromatosis) Arthralgias Abdominal discomfort Insulin resistance and diabetes mellitus (50% of patients with hereditary hemochromatosis) Erectile dysfunction in men (45% of patients with heretditary hemochromatosis) Amenorrhea[faculty.washington.edu]

Workup

The following investigations are helpful in establishing the diagnosis of hemochromatosis.

  • Serum ferritin and iron concentration: Evaluation of the serum in the patients of hemochromatosis shows an increase in the amount of ferritin and iron concentration.
  • Serum iron binding capacity: The patients of hemochromatosis have a reduced serum iron binding capacity.
  • Biopsy of the liver: Upon the biopsy and histopathological examination of the hepatic tissue, heavy iron deposition along with fibrosis of the tissue is seen.
  • Other tests:  Once hemochromatosis is confirmed, other tests will be required to find out whether or not the hemochromatosis is secondary to hemolytic disorders, multiple blood transfusions or dietary iron overload.
Ferritin Increased
  • In 1983, haemochromatosis was suspected because of abnormal skin pigmentation at the age of 60 years and confirmed by an elevated serum ferritin, increased transferrin saturation, and increased iron stores with micronodular cirrhosis on liver biopsy.[doi.org]
HLA-A3
  • […] ancestry are homozygous for mutation; 1/11 are heterozygous; thus disease is very common Pathophysiology Due to mutation on transferrin receptor binding protein HFE (formerly called HLA-H) on 6p, close to HLA gene and in linkage disequilibrium with HLA-A3[pathologyoutlines.com]
  • . : Association of HLA A3 and HLA B14 antigens with idiopathic hemochromatosis. Gut 1976, 17:332–334. PubMedCentral PubMed CrossRef Google Scholar 7.[link.springer.com]
  • Fauchet Association of HLA-A3 and HLA-B14 antigens with idiopathic hemochromatosis Gut, 17 (1976), pp. 332-334 [6.] M. Simon, M. Bourel, B.[archbronconeumol.org]
  • The gene for HH is closely linked to the HLA-A3 locus on the short arm of chromosome 6 [ PMID 1278715 ]. In 1996, HFE, a gene for HH, was found to have two missense mutations [ PMID 8696333 ].[snpedia.com]
  • This gene is closely linked to the HLA-A3 locus.[en.wikipedia.org]
Liver Biopsy
  • We recommended liver biopsy for subjects with serum ferritin levels of 300 ng per milliliter or higher. The subjects were followed for up to four years.[ncbi.nlm.nih.gov]
  • Eleven of the 16 underwent liver biopsy. Three of the five who did not (Subjects 3, 11, and 12) did not meet the criteria for liver biopsy and had serum ferritin levels of 100 ng per milliliter or less.[doi.org]
  • Confirmation of this disorder is accomplished with genetic testing and liver biopsy. Treatment should commence immediately and undergo venesection (phlebotomy) treatments 2 to 4 times a year for the remainder of the patient's life.[ncbi.nlm.nih.gov]
  • The serum α-fetoprotein concentration was within the range of normal, and repeated liver biopsy did not show histomorphologic signs of malignancy but confirmed the presence of IFF in surrounding siderosis.[ncbi.nlm.nih.gov]
  • Liver Biopsy During a liver biopsy, your doctor numbs an area near your liver and then removes a small sample of liver tissue using a needle. The tissue is then looked at under a microscope. A liver biopsy can show how much iron is in your liver.[nhlbi.nih.gov]
Hepatocellular Carcinoma
  • It is very rare to see hepatocellular carcinoma in the absence of evidence of liver injury.[ncbi.nlm.nih.gov]
  • Studies have shown that excessive iron deposits in the liver due to hereditary hemochromatosis leads to cirrhosis, which can put an individual at increased risk for developing hepatocellular carcinoma.[ncbi.nlm.nih.gov]
  • Hepatocellular carcinoma (HCC) is a long-term complication of HH, which contributes to increased mortality.We evaluated the risk factors of HCC in a prospective cohort of Swiss hemochromatosis patients with a long-term follow-up.We included 147 patients[ncbi.nlm.nih.gov]
  • Untreated hemochromatosis can lead to chronic liver disease, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Many invasive and noninvasive diagnostic tests are available to aid in diagnosis and treatment.[ncbi.nlm.nih.gov]
  • Markus.Quante@medizin.uni-leipzig.de Abstract Hepatocellular carcinoma (HCC) commonly develops in cirrhotic or noncirrhotic livers affected by congenital hemochromatosis.[ncbi.nlm.nih.gov]

Treatment

Hemochromatosis is treated according to the following principles.

  • Dietary modifications: The patients of hemochromatosis should maintain a diet that is very low in iron. Red meat, alcohol and vitamin C should be avoided.
  • Phlebotomy: Phlebotomy refers to the removal of blood from the veins. It is an effective procedure for the reduction of iron overload in the patients suffering from hemochromatosis [9]. Removal of 500 ml of blood removes upto 250 mg of iron. This should be done weekly until the amount of iron in the serum returns to normal; which may take as long as two years. Once the amount of ferritin in the serum becomes less than 50 micrograms per liter, phlebotomy is performed after every 2 to 4 months for maintenance.
  • Chelation: A chelating agent such as deferoxamine helps in controlling overload of iron in the patients of hemochromatosis. Deferoxamine is given through an intermittent infusion. If the patient can not tolerate phlebotomy (because of any underlying condition such as anemia or heart failure), continuous infusion of deferoxamine may be required.

For the treatment of complications, surgical intervention may be needed. Liver transplantation is necessary in end stage liver disease and surgical arthroplasty is required in case of severe arthropathy [10].

Prognosis

The prognosis of the patients suffering from hemochromatosis is not good [7]. Phlebotomy improves the prognosis at any stage of the disease. If hemochromatosis is detected early, phlebotomy may help prevent cirrhosis. If cirrhosis has already occurred, phlebotomy is still helpful in reducing the complications of the cirrhosis such as variceal bleeding from the esophagus. Up to 23% of the patients suffering from hepatic cirrhosis due to hemochromatosis develop hepatocellular carcinoma [8].

Etiology

Depending upon the etiology, hemochromatosis can be classified as primary and secondary. Primary or idiopathic hemochromatosis is an inherited disease with an autosomal-recessive pattern. The defective gene is named HFE and is present on the short arm of chromosome 6 [2] [3]. Other mutations have been described in rare cases.

Secondary causes of iron overload are hemolytic anemias such as thalassemia in which multiple blood transfusions are required [4].

Epidemiology

In the United States, the prevalence of hemochromatosis is 1 in 200 to 500 individuals. It is the most common autosomal-recessive inherited disease [5]. Hemochromatosis usually occurs in men above the age of 50 years.

Women are affected much less commonly as the loss of iron in menstrual bleeding prevents the accumulation of iron. Hemochromatosis is 6 times more common in whites as compared to blacks.

Sex distribution
Age distribution

Pathophysiology

The normal iron content of the body is 3 to 4 grams. In hemochromatosis, there is excessive iron deposition in many organs throughout the body including the liver, pancreas, heart, adrenals, testes, pituitary and the kidneys. The iron is deposited in the form of hemosiderin. Deposition of hemosiderin causes fibrosis and functional failure of these organs which manifest as signs and symptoms of the disease [6].

In symptomatic hemochromatosis, the total iron content of the body is around 20 to 40 grams. In the pancreas and liver, the iron content may even be up to fifty to hundred times that of normal.

Prevention

There is no effective preventive measure against the development of primary hemochromatosis. Secondary hemochromatosis can be prevented by prompt anticipation or diagnosis of any condition that could cause overload of iron (such as multiple blood transfusions and hemolytic anemias such thalassemia). Precautions can then be taken to reduce the likelihood of accumulation of iron.

Summary

Hemochromatosis is the condition in which there is excessive accumulation of iron in all the body tissues, particularly the liver, pancreas, heart, kidney and pituitary gland [1].

Hemochromatosis may be idiopathic or may result from secondary causes of iron overload. The patients present with deep bronze pigmentation of the skin. Liver cirrhosis and diabetes due to secondary pancreatic insufficiency are the most common features. The treatment of hemochromatosis consists of phlebotomy and chelation therapy.

Patient Information

Hemochromatosis is a condition in which the amount of iron in the body is increased. It accumulates in various organs of the body and interferes with their function. The patients usually have bronze discoloration of the skin along with failure of the liver and pancreas. The prognosis of the patients suffering from hemochromatosis is not very favorable.

References

Article

  1. Fleming RE, Sly WS. Mechanisms of iron accumulation in hereditary hemochromatosis. Annual review of physiology. 2002;64:663-680.
  2. Bittencourt PL, Marin ML, Couto CA, Cancado EL, Carrilho FJ, Goldberg AC. Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis. Clinics. 2009;64(9):837-841.
  3. Himmelmann A, Fehr J. Cloning of the hereditary hemochromatosis gene: implications for pathogenesis, diagnosis, and screening. The Journal of laboratory and clinical medicine. Mar 1999;133(3):229-236.
  4. Gattermann N. The treatment of secondary hemochromatosis. Deutsches Arzteblatt international. Jul 2009;106(30):499-504, I.
  5. McCullen MA, Crawford DH, Hickman PE. Screening for hemochromatosis. Clinica chimica acta; international journal of clinical chemistry. Jan 2002;315(1-2):169-186.
  6. Worwood M. Pathogenesis and management of haemochromatosis. British journal of haematology. Apr 1999;105 Suppl 1:16-18.
  7. Niederau C, Strohmeyer G, Stremmel W. Epidemiology, clinical spectrum and prognosis of hemochromatosis. Advances in experimental medicine and biology. 1994;356:293-302.
  8. Milman N, Pedersen P, a Steig T, Byg KE, Graudal N, Fenger K. Clinically overt hereditary hemochromatosis in Denmark 1948-1985: epidemiology, factors of significance for long-term survival, and causes of death in 179 patients. Annals of hematology. Dec 2001;80(12):737-744.
  9. Strohmeyer G. [Treatment of primary idiopathic hemochromatosis and secondary hemosiderosis]. Deutsche medizinische Wochenschrift. Nov 8 1974;99(45):2295-2299.
  10. Khanna A, Jain A, Eghtesad B, Rakela J. Liver transplantation for metabolic liver diseases. The Surgical clinics of North America. Feb 1999;79(1):153-162, ix.

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Last updated: 2018-06-22 09:13