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Hemochromatosis is a syndrome which, when fully expressed, is manifested by melanoderma , diabetes mellitus, and liver cirrhosis, with iron overload involving parenchymal and reticuloendothelial cells in many organ systems. This clinical presentation may arise as a consequence of either hereditary or acquired abnormalities of iron overload, although the mechanisms are quite different. In hereditary hemochromatosis (also known as primary, or idiopathic, hemochromatosis), increased intestinal iron absorption leads to excessive accumulations of iron, throughout the body, particularly in parenchymal cells. In secondary forms of iron overload including transfusional hemosiderosis, alcoholic cirrhosis, thalassemia, sideroblastic anemia, and porphyria cutanea tarda, iron accumulates in the reticuloendothelial system initially, but with increasing amounts of total body iron, excessive iron deposits eventually accumulate in parenchymal cells throughout the body producing a picture indistinguishable from hereditary hemochromatosis. In this article, the course, prognosis, and therapy of iron overload will be reviewed in detail. Clinical and experimental data concerning the pathogenesis of the different forms of iron overload will be examined critically. In particular, information relating to possible abnormalities of reticuloendothelial function, intestinal mucosal iron transport, and alterations in serum and tissue isoferritin patterns in hereditary hemochromatosis will be analyzed, and possible directions for future research will be suggested. The mode of inheritance and linkage with the major histocompatibility (HLA) complex will be discussed. Theories on the pathogenesis of tissue damage by excess iron will be evaluated. Methods for measuring the extent of iron overload in clinical practice will be described, including measurements of serum iron, serum ferritin, iron absorption, cobalt excretion, desferrioxamine excretion, liver biopsy and tissue iron determinations, and HLA typing. Finally, unresolved problems in the understanding of the disease process, diagnosis, and therapy will be delineated.
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PMID:Iron overload disorders: natural history, pathogenesis, diagnosis, and therapy. 637 41

A 54 year-old previously healthy woman was admitted with staphylococcus aureus septicaemia. The patient had been treated with oral iron supplementation for two years due to fatigue. In the evaluation of postinfectious anaemia, serum transferrin saturation and serum ferritin were found persistently elevated with values of 74% and 950 micrograms/1, respectively. Hereditary haemochromatosis was suspected even though there was no history of liver disease or diabetes mellitus in the family. A bone marrow biopsy showed a normal content of haemosiderin iron. The liver biopsy revealed haemosiderosis, mainly located to the periportal hepatocytes, and fibrosis in the portal tracts. The HLA-type was A3, B7, B37. Over a period of ten months, a total of 3.9 g of iron was removed by venesection while S-ferritin declined to 31 micrograms/l. A sister to the proband had an identical HLA type, but normal iron status markers, either indicating heterozygosity or homozygosity with lack of penetrance. In preclinical hereditary haemochromatosis, early diagnosis and treatment is essential in order to prevent organ damage and to improve prognosis. Prophylactic screening is recommended. The identification of one homozygous subject in a Danish year-cohort of 60.000 persons costs approximately 40.000 Danish kroner (7.000 US+).
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PMID:[Preclinical hereditary hemochromatosis--is there an indication for preventive screening?]. 765 9

Idiopathic hemochromatosis, the most frequent inherited disease in Caucasians, is frequently undiagnosed. In this disorder, characterized by a continued inappropriated absorption of dietary iron, the clinical manifestations result from damage to those organ systems in which iron has been pathologically deposited, namely, the heart and the liver. Typically, hemochromatosis becomes clinically manifest in later life and in men more frequently than in women. This has been attributed to the extra loss of iron in women through menstruation and pregnancies. Removal of the excess iron by phlebotomy will prevent all of the complications of hemochromatosis of when begun early. In this paper, we report a case of a young woman with a eight years evolution of amenorrhea, cardiac failure, diabetes mellitus and increased pigmentation of the skin, associated with biochemical markers of iron overload. It is emphasized that hemochromatosis most be excluded in all patients with a unexplained cardiac failure.
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PMID:[Refractory heart failure in a 26-year-old woman with idiopathic hemochromatosis]. 783 64

Hereditary hemochromatosis is a common disorder of iron metabolism with a prevalence as high as 8 per 1000. Affected individuals absorb excessive amounts of dietary iron and over time, tissue iron deposition results in skin discoloration, arthropathy, hepatic cirrhosis, heart failure, diabetes mellitus and impotence. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening. This conclusion is supported by cost-effectiveness analysis based on available data. A reasonable screening strategy would start with a serum transferrin saturation. A value > or = 55% should trigger a repeat transferrin saturation in a fasting state and a serum ferritin level. If both these tests are abnormal, a liver biopsy with quantitative iron determination is the currently accepted confirmatory test.
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PMID:Management of hereditary hemochromatosis. 788 27

Hereditary hemochromatosis is a prevalent inherited disorder with an estimated frequency of homozygosity of 0.2 to 0.45% in Caucasians. The disease is characterized by progressive iron overload until a massive accumulation of body iron occurs. Undetected, the disorder eventually can produce either cirrhosis, diabetes mellitus, cardiac disease, arthritis, or hepatocellular carcinoma or a combination of these manifestations. Early diagnosis and treatment prevents organ damage and normalizes life expectancy. Screening studies to detect hemochromatosis are most effectively accomplished by measurement of the serum iron and total iron binding capacity. Treatment is most effectively performed by frequent phlebotomy until body stores are empty and then 3 to 4 times yearly for life. The basic defect of hemochromatosis appears to increase iron absorption, decrease iron excretion, and produce preferential deposit of iron in hepatic parenchymal cells rather than Kupffer cells. The genetic abnormality of hemochromatosis is located on chromosome 6 in close association with the gene for HLA antigens. Recent speculation postulates that tumor necrosis factor may be involved in the etiology of this disease because of its location on chromosome 6 and its effect upon iron transport.
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PMID:Hereditary hemochromatosis: a prevalent disorder of iron metabolism with an elusive etiology. 794 87

Primary hemochromatosis is characterized by a specific pattern of clinical manifestations. It includes liver disease with hepatomegaly, glucose intolerance, e.g. diabetes, hyperpigmentation oft the skin, impotence/ amenorrhea, arthropathy, cardiomyopathy and fatigue. Laboratory investigation reveals significantly elevated serum ferritin and transferrin saturation with iron. The diagnosis is confirmed by liver biopsy and quantitative determination of elevated liver iron content. Wilson's disease represents a copper storage disease. Prominent clinical features are hepatomegaly and splenomegaly. Neurological alterations and detection of Kayser-Fleischer corneal rings are typical. In the acute initial phase the often young patients present with Coombs-negative hemolysis. Psychiatric alterations, cardiomyopathy, arthropathy, nephropathy, as well as thrombocytopenia and leucopenia are other clinical features. Laboratory parameters of Wilson's disease include low serum ceruloplasmin and serum copper. There is an elevated urinary copper excretion and elevated serum free copper concentration. The diagnosis is confirmed by liver biopsy with quantitative determination of an elevated liver copper content.
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PMID:[Current diagnosis: hereditary metabolic diseases of the liver (primary hemochromatosis, Wilson disease)]. 898 78

Approximately 1.5 million persons in the United States are affected by iron overload diseases, which are primarily caused by hereditary hemochromatosis--the most common genetic disorder in the United States. Hereditary hemochromatosis is characterized by increased iron absorption in the gastrointestinal tract, which may cause lifelong excessive iron absorption and accumulation and serious health effects, including arthritis, cirrhosis, diabetes, impotence, heart failure, and death. Hereditary hemochromatosis is an autosomal recessive disease; the estimated prevalence of the homozygous genotype is 1:200 - 1:250 persons, and 10% of persons are carriers. Although the disease was previously believed to affect primarily white males of northern European descent, recent data indicate hereditary hemochromatosis also occurs among blacks. Moreover, iron overload diseases are underdiagnosed among whites and may not be considered in other racial/ethnic groups (e.g., Hispanics) even when compatible symptoms and clinical findings are present. As part of a joint demonstration project during August-October 1995 to determine the overall prevalence of iron overload, CDC reviewed data from a health-maintenance organization (HMO) in San Diego, California; the prevalence among Hispanics appeared similar to that for non-Hispanic whites. This report presents the preliminary findings of an analysis of the prevalence of iron overload among Hispanics and compares these findings with nationally representative data from the Third National Health and Nutrition Examination Survey (NHANES III). These findings indicate that the prevalence of possible iron overload among Hispanic clients of the HMO based on initial screening was consistent with the nationwide prevalence of possible iron overload based on a single screening test for Hispanics of Mexican descent and non-Hispanic whites.
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PMID:Iron overload disorders among Hispanics--San Diego, California, 1995. 900 7

Hereditary hemochromatosis (HHC) is an inherited disease transmitted in an autosomal recessive pattern. With homozygosity occurring in up to 0.5% of the population, HHC is the most prevalent genetic disease among the white population worldwide and has the same prevalence as the sickle cell trait in the African-American population. An asymptomatic 50-year-old white man presented at the family practice clinic and stated that HHC had been diagnosed in his mother. Laboratory findings showed markedly elevated transferrin saturation and ferritin levels. The diagnosis of HHC was made on the basis of the laboratory results and family history, and therapy was begun. Clinical manifestations of HHC occur late and include diabetes mellitus, cirrhosis, and cardiomyopathy. As end-organ damage is preventable, optimal management involves early diagnosis and lifelong phlebotomy. Diagnosis is made by an elevated transferrin saturation level and an increased serum ferritin value. Hereditary hemochromatosis is a genetic disorder of iron metabolism that has an excellent prognosis if diagnosed early.
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PMID:Hereditary hemochromatosis. 907 Dec 52

Our objective was to study the predictive value of the family history in the initial diagnosis of hereditary hemochromatosis. Sixty five hemochromatosis proband patients and 66 control patients with chronic liver disease were assessed for a family history of hemochromatosis, cirrhosis, diabetes, and arthritis. There were no significant differences in the frequency of cirrhosis, diabetes, and arthritis between hemochromatosis patients and control patients. A family history of hemochromatosis was present in 3.6% of hemochromatosis patients and none of the control patients. Multivariate discriminative analysis demonstrated that the combination of cirrhosis, diabetes, and arthritis could only predict the diagnosis of hemochromatosis in 48% of cases. We conclude that a family history of cirrhosis, arthritis, and diabetes is not more common in hemochromatosis patients compared to control patients with chronic liver disease.
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PMID:Predictive value of family history in diagnosis of hereditary hemochromatosis. 920 Nov

Chronic mild liver enzyme abnormalities are attributable to hereditary hemochromatosis in at least 3% of cases. Hemochromatosis formerly was diagnosed late with diabetes and hepatic and cardiac failure. Only recently have the autosomal recessive inheritance and subtle early presentations been understood. However, patients still wait many years and see many physicians before receiving a correct diagnosis. Increased serum transferrin saturation is currently the best test for detection of those likely to accumulate iron. Serum ferritin identifies those requiring treatment. When liver biopsy (controversial in asymptomatic individuals) is indicated, chemical measurement of liver iron content is helpful and therapeutic phlebotomy is the only effective treatment. Caucasian-type hemochromatosis (prevalence of 0.005) is associated with genetic abnormalities in HLA-H but also occurs in other ethnic groups. Those of African descent may have a different but also heritable iron-loading disease. Caucasian-type and to a lesser extent African iron loading are detectable early by laboratory testing. Early treatment restores normal expectations of length and quality of life in the Caucasian disease. Long-term treatment data are not yet available in African iron loading. Laboratory-initiated screening programs using unsaturated iron-binding capacity can eliminate symptomatic hemochromatosis.
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PMID:Mild liver enzyme abnormalities: eliminating hemochromatosis as cause. 926 5


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