[Deliberations on hemochromatosis. Apropos of 3 cases of idiopatic hemochromatosis].
Explore the source record for details and available documents.
Adult↗
SEARCH · PubMed Health
Results for “Hemochromatosis”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Idiopathic hemochromatosis. Demonstration of recessive transmission and early detection by family HLA typing.
We studied iron overloading and HLA types in 24 sibships of patients with idiopathic hemochromatosis, of which 15 had at least two subjects with overt forms. HLA types of 84 unrelated patients were also investigated. Among siblings there was a significant association (P less than 0.0001) between the presence of hemochromatosis and the possession of the same two HLA haplotypes. The fact that overt forms of hemochromatosis depend on the presence of two specific homologous chromosomes strongly supports a recessive mode of transmission for the overt disease. The haplotypic equilibrium demonstrated in the unrelated patients group is another supporting argument. The lod-score value (2.239 for theta = 0.005) in six families available for study further supports the conclusion that a hemochromatosis gene is closely linked to the HLA-A locus. HLA typing in families with hemochromatosis could provide a means of early detection of subjects at risk before appearance of any sign of iron overload.
Adult↗
Hypovitaminemia A in idiopathic hemochromatosis and hepatic cirrhosis. Role of retinol-binding protein and zinc.
Serum levels of vitamin A, its specific carrier protein retinol-binding protein (RBP), and zinc were determined in 34 cases of idiopathic hemochromatosis, 33 cases of alcoholic cirrhosis, 10 cases of non-alcoholic cirrhosis, and in 35 normal controls. In both alcoholic and non-alcoholic cirrhosis, vitamin A and RBP levels were very significantly reduced, whereas a significantly low zinc was observed only in the alcoholic cirrhosis group. In idiopathic hemochromatosis, vitamin A values were significantly lower compared to normals, whereas serum RBP levels were normal and serum zinc was very close to that of the controls. A significant correlation was found between vitamin A and RBP levels in the entire group of 112 patients. These results, (1) in alcoholic and non-alcoholic cirrhosis, confirm a dramatic vitamin A deficiency and the major role played by decreased RBP, but tend to deemphasize the possible role of zinc deficiency; (2) in idiopathic hemochromatosis, affirm a significant serum vitamin A deficiency supposedly by a different mechanism from that of alcoholic cirrhosis since in idiopathic hemochromatosis plasma RBP levels are normal. The role of this vitamin A disorder should be considered in the interpretation of clinical signs of idiopathic hemochromatosis such as ichthyosis and visual disorders.
Adult↗
Hemochromatosis: a disease often silent but not invisible.
Hemochromatosis is a disorder characterized by the association of portal cirrhosis with deposition of excess amounts of iron in the parenchymal cells of many organs. Arthralgia and arthritis occur in about 50% of patients. The role of the radiologist is often significant in the recognition of this condition because hemochromatosis may be unsuspected clinically since the hepatic cirrhosis is frequently inactive at the time the arthritis develops. The possibility of hemochromatosis should be considered when the characteristic involvement of the metacarpophalangeal, radiocarpal, and proximal interphalangeal joints of the hand and wrist is present. In addition, articular and fibrocartilage calcification is often noted, particularly in the knee, triangular cartilage of the wrist, hip, elbow, symphysis pubis, and shoulder. Although localized chondrocalcinosis may be seen in association with many disorders, as well as in asymptomatic elderly persons, generalized chondrocalcinosis is a significant finding and is commonly associated with hemochromatosis. Recognition of the typical distribution of the arthropathy plus its characteristic roentgenographic features should aid in the identification of patients with the disorder who do not demonstrate the typical clinical features of hemochromatosis.
Arthritis↗
Histocompatibility antigens as markers of abnormal iron metabolism in idiopathic hemochromatosis.
To determine the frequency of HLA histocompatibility antigens in persons with idiopathic hemochromatosis and their usefulness as genetic markers of the disease, HLA typing for the A, B and C loci was carried out. HLA-A3 was found in 61% of 18 unrelated individuals with idiopathic hemochromatosis compared with 25% of 253 randomly chosen control subjects (P less than 0.001), and HLA-B7 was found in 50% and 22% respectively (P less than 0.025). Eighty-six members of seven families with idiopathic hemochromatosis were screened for abnormalities in iron metabolism with tests for serum iron concentration, transferrin saturation, serum ferritin concentration and iron content of the hepatocytes. Of the 14 persons selected for liver biopsy because of abnormalities detected by these tests, 8 had increased amounts of stainable iron in the hepatocytes. Body iron overload was subsequently demonstrated in six of the seven, who had undergone repeated phlebotomy. In sibships having one member with hemochromatosis, only 1 of 22 members had two haplotypes in common with the proband, whereas in sibships having more than 1 member with the disease 4 of 5 affected members had two haplotypes in common. HLA typing in families with hemochromatosis may provide a means of identifying persons at risk of acquiring the disease.
Epitopes↗
Serum ferritin as a possible marker of the hemochromatosis allele.
To determine whether a correlation exists between the biochemical expression of hemochromatosis and the HLA genotype, we studied 174 family members of 32 persons with the disease. Persons who shared both HLA haplotypes with the proband (and presumably having two hemochromatosis alleles) differed significantly from those who shared only one haplotype (and presumably having one hemochromatosis allele) in terms of serum iron (P less than 0.001 for both sexes), unsaturated iron-binding capacity (P less than 0.01 for female and P less than 0.0001 for male subjects) and serum ferritin (P less than 0.0001 for female and P less than 0.00001 for male subjects). The only significant difference between relatives having one hemochromatosis allele and age and sex-matched controls was related to serum ferritin values in male subjects (P less than 0.05, despite considerable overlap). In our hands, serum ferritin was the best indicator of disordered iron metabolism and was elevated among most homozygous but among few heterozygous family members.
Adolescent↗
Ascorbic acid status in idiopathic hemochromatosis.
Vitamin C status was studied, by means of leucocyte ascorbic acid concentrations, in 67 cases of idiopathic hemochromatosis subdivided into 44 untreated and 25 treated cases (2 patients belonging to both subgroups) and compared to 31 normal subjects and 37 alcoholic cirrhosis patients. The control groups exhibited the following mean levels (+/- SEM): 34.4 +/- 1.9 microgram/10(8) WBC in normals and 22.0 +/- 1.8 microgram/10(8) WBC in alcoholic cirrhosis. In idiopathic hemochromatosis the mean levels were: for the untreated group 19.5 +/- 1.7 microgram/10(8) WBC and for the treated group 34.3 +/- 2.3 microgram/10(8) WBC. These results (1) affirm an important vitamin C deficiency in the untreated disease; (2) suggest that iron overload is the main causal factor in view of the striking difference--to date unreported--between untreated and treated cases of idiopathic hemochromatosis. Besides its possible theoretical interests, this vitamin C deficiency is responsible in idiopathic hemochromatosis for a significant underestimation of the desferrioxamine-induced urinary iron excretion.
Adult↗
The triad of hemochromatosis, hepatoma and erythrocytosis.
The triad of hemochromatosis, hepatoma and erythrocytosis is a rare combination. Hemochromatosis is often not recognized until the patient presents with the symptoms of hepatocellular carcinoma and erythrocytosis, and the development of erythrocytosis is an important clue to the under-lying hepatoma. The high serum iron concentration and the high saturation of the iron-binding protein, as well as the typical bone marrow hemosiderin pattern, are important aids in the recognition of hemochromatosis. To date, all patients with this triad have been elderly males. The clinical course is usually one of rapid deterioration and death. The seven previously reported cases have been reviewed and the relationship of the erythrocytosis to the increased production of erythropoietin is discussed.
Aged↗
Reduced chromium retention in patients with hemochromatosis, a possible basis of hemochromatotic diabetes.
Chromium (III) has recently been shown to be an essential trace mineral in rats, being required for normal function of insulin in controlling glucose metabolism. Chromium is transported in the body bound to transferrin, where it binds competitively with iron. Hemochromatosis is an iron storage disease in humans characterized by highly saturated transferrin levels and sometimes by diabetes. We postulated that the diabetes may be due to exclusion of chromium by iron at metabolic binding sites. 51Cr(III) was administered i.v. to 5 normal males, 6 patients with hemochromatosis prior to therapeutic removal of iron, and 5 patients with varying levels of iron loading. The retention of 51Cr was measured with a whole-body counter for 8 mo and blood levels were measured for 40--80 days. Analysis of the whole-body retention curves revealed 3 exponential components with T1/2s of .56 days, 12.7 days, and 192 days; the blood curves had 4 components with T1/2s of 13 min; 6.3 hr, 1.9 days, and 8.3 days. The T1/2s were not significantly different between the normals and patients. The coefficients of these components however, were significantly lower for the long T1/2 components in the iron-loaded patients, demonstrating reduced retention of 51Cr as postulated. Whether this reduced retention of chromium is causally related to diabetes in hemochromatosis and whether abnormal chromium metabolism is involved in endogenous diabetes, thus, becomes an important question for future study.
Adult↗
Hemochromatosis. Pathophysiologic and genetic considerations.
The clinical, genetic, and pathologic findings, and the pertinent case histories in two families with idiopathic hemochromatosis are presented. These studies support the view that idiopathic hemochromatosis is a disease inherited in at least two ways. In one of these families, inheritance appeared to occur in an autosomal recessive manner, whereas in the other, autosomal dominant expression seemed evident. Evidence that an inability of the reticuloendothelial cells to handle iron may play a major role in the pathogenesis of hemochromatosis is presented. The early age of onset and poorer prognosis associated with the recessive inheritance suggest that the defect in reticuloendothelial cell function present in such cases is different from or more severe than those associated with dominant inheritance.
Adolescent↗
Hemochromatosis caused by excessive vitamin iron intake.
Rare cases of hemochromatosis have been reported in patients who underwent prolonged oral iron therapy for hemolytic anemia or prolonged self-treatment with iron pills. A proportionately large segment of the South African Bantu tribe, who ingest large quantities of an alcoholic beverage brewed in iron pots, are found to have the disease. Reports of health fadists developing hemochromatosis due to excessive dietary iron intake, however, are extremely rare. This report presents clinical considerations and pathologic findings in a compulsive health fadist who consumed large numbers of vitamins containing iron. Clinical findings included the development and progression of cirrhosis of the liver, bronzing of the skin, and diabetes mellitus, all consistent with a diagnosis of hemochromatosis. Light microscopy of liver biopsies taken late in the course of the disease revealed a massive buildup of iron in the hepatocytes, less in the Kupffer cells, and sparse deposition in the epithelial cells of the bile duct. Minimal periportal fibrosis was noted. Electron microscopy showed numerous pleomorphic siderosomes with varying degrees of crystallization and ferritin attached at uniform intervals to the membranes of residual bodies. Abundant free ferritin was observed in most cells. The aggregated and membrane-associated ferritin was verified by non-dispersive x-ray analysis. An additional finding, noted only by electron microscopy, was the presence of many fat-storing cells of Ito, which are thought to be involved in the onset of fibrosis.
Cytoplasmic Granules↗
Genetic linkage between hereditary hemochromatosis and HLA.
A large Mormon pedigree of a proband with hemochromatosis was studied, using transferrin saturation as the quantitative phenotypic trait. The analysis indicated that the inheritance of hemochromatosis was recessive, with partial expression in some heterozygotes. The lod score of 6.88 (theta = .0) was strongly indicative of linkage between the hemochromatosis locus and the human major histocompatibility (HLA) loci.
Chromosome Mapping↗
Deferoxamine-chelatable iron in hemochromatosis and other disorders of iron overload.
Deferoxamine-chelatable iron was measured in 103 patients with known or suspected iron overload. All of 34 patients with untreated hemochromatosis had distinctly elevated values for deferoxamine-chelatable iron. The mean value in these cases was significantly greater than that in patients with cirrhosis, who had little or no stainable hepatic iron. In 15 patients with hemochromatosis who were tested sequentially during the course of phlebotomy therapy, deferoxamine-chelatable iron proved a reliable index of the degree of reduction of storage iron. In 22 additional patients with partially treated hemochromatosis and 14 with iron overload accompanying chronic anemia, this test correlated well with the magnitude of iron deposits in liver or bone marrow. In patients with unexplained elevations of serum iron, normal or only slightly elevated deferoxamine-chelatable iron correctly indicated that storage (hepatic) iron was not excessive. The test was more reliable than determination of serum iron or transferrin saturation as an indicator of increased storage iron. Elevated values could not be attributed to disturbed liver function. Determination of deferoxamine-chelatable iron is a safe, practical, and useful procedure for identifying persons with increased iron stores and for assessing the effect of phlebotomy therapy.
Adult↗
Preclinical hemochromatosis in a population on a high-iron-fortified diet.
Three hundred forty-seven (96.4%) of all persons aged 30 to 39 years were screened with serum iron and iron binding capacity measurements to determine the incidence of hemochromatosis in a population. No women had signs of iron overload; however, nine men (5%) had persistenly elevated serum iron levels. In four men (2%), increased iron stores was found with a distribution like that in the early stages of hemochromatosis. In combination with recent findings of clinical hemochromatosis at our hospital, this study suggests that this condition is not as rare as has been reported earlier.
Adult↗
Familial hemochromatosis: characteristics of the precirrhotic stage in a large kindred.
Ffty asymptomatic members of a kindred with familial hemochromatosis were studied in an effort to clarify some of the physiologic abnormalities present in the pre-cirrhotic or latent stage of the disease. Using excess hepatic iron as a marker for inheritance of hemochromatosis, results of liver biopsies on 31 family members suggest an auto-somal dominant mode of inheritance with incomplete expressivity. In addition to a relationship between alcohol intake and excess liver iron, there was a strong association between the level of alcohol intake and the presence of hepatic fibrosis in those subjects with excess iron stores. Both serum iron and transferrin saturation were significantly higher in family members with iron overload than in those who were not affected. Only transferrin saturation was significantly correlated with the severity of hepatic iron deposition. Studies of glucose tolerance (OGTT, IVITT, glucose clamp studies) demonstrated a defect in carbohydrate metabolism associated with deficient insulin secretion and insulin resistance, both of which were related to the degree of hepatic iron depostion. In this kindred we have found no evidence for a contribution of inheritance to the carbohydrate intolerance of hemochromatosis. Iron overload was not related to activity of hepatic collagen proline hydroxylase or urinary excretion of peptide-bound hydroxyproline. Serum ferritin, previously thought to be a reliable marker of reticuloendothelial iron stores, was normal in 19 of 20 family members with iron overload.
Adolescent↗
[Study of glucagon secretion in patients with hemochromatosis].
Diabetes in idiopathic hemochromatosis has been considered to be secondary to islet cell damage resulting from the iron deposits. Plasma glucagon was measured by immunoassay using the pancreas specific 30-K antiserum, and was found to be normal or slightly elevated during arginine-infusion tests in patients exhibiting both hemochromatosis and pathological glucose tolerance. This suggests that diabetes in hemochromatosis is not due to a lesion resulting from the iron deposits. The two affections appear to be merely associated and are possibly genetically linked.
Diabetes Mellitus↗
Patterns of iron storage in dietary iron overload and idiopathic hemochromatosis.
Bone marrow iron stores rise in proportion to the total body iron store in dietary iron overload. The situation in the genetic disorder of idiopathic hemochromatosis is not as clear. A method for measuring the storage iron concentration chemically on samples of bone marrow obtained by trephine needle biopsy was therefore developed. Its value as a measure of tissue iron stores was established in a preliminary investigation in which specimens of liver, spleen, and bone marrow were obtained at necropsies on 66 South African Negroes among whom dietary iron overload is common. A wide range of nonheme iron concentrations was found, but in each individual there was a highly significant correlation between the concentrations in the three tissues. Nonheme iron concentrations were then determined on trephine bone marrow biopsy specimens from eight Caucasian patients with untreated idiopathic hemochromatosis, and on percutaneous liver biopsy specimens from four of them. The concentrations in the livers were in the anticipated range of 5,000 mug per gram wet weight (2 per cent dry weight). In contrast the geometric mean value for bone marrow iron concentration was 186 mug per gram wet weight, a figure that fell below the fiftieth percentile for marrow iron concentrations in the South African Negroes, whereas the geometric mean liver iron concentration was above the ninetieth percentile. These findings indicate that subjects with idiopathic hemochromatosis whose liver iron stores are grossly increased do not show a comparable rise in bone marrow iron stores.
Adult↗
Familial hemochromatosis. Physiologic studies in the precirrhotic stage of the disease.
We studied 12 members of a family with precirrhotic hemochromatosis to define the physiologic abnormalities in the asymptomatic phase of the disease. Six of 12 had increased iron stores; the mode of inheritance was consistent with an autosomal dominant trait. Serum ferritin levels were no more predictive of tissue iron levels than measurements of serum iron, transferrin saturation or chelatable iron excretion. In three affected family members intestinal iron content was normal. Liver proline hydroxylase activity and urinary hydroxyproline excretion did not correlate with tissue iron content, suggesting that, in addition to the possible role of tissue iron, hepatic fibrosis may involve other factors. "Borderline diabetes mellitus" was present in three affected family members, but extensive studies revealed that pituitary dysfunction is uncommon in early hemochromatosis. Increased levels of liver iron proved to be the most reliable marker for the disease.
Adolescent↗