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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the case of a 14-year-old girl who originally presented at the age of eight with a history of bloody stools, abdominal pain and weight loss. Initial iron studies showed raised serum iron and transferrin saturation but low ferritin and were interpreted as consistent with iron deficiency under treatment. As she had not taken any supplemental iron she later underwent genetic testing for the Cys282Tyr and His63Asp mutations of the HFE gene. On the basis of these results, she was diagnosed as having hereditary haemochromatosis (HH). This case highlights that a low serum ferritin does not exclude the diagnosis of HH and that the availability of genetic testing can now enable probands and affected family members to be identified.
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PMID:Interpretation of iron studies in adolescent haemochromatosis. 1034 73

HFE is a non-typical MHC class 1-type protein that is mutated in hereditary hemochromatosis. The purpose of this study was to identify possible splice variants of HFE mRNA and investigate the regulation of these isoforms in duodenum and liver of patients with normal and altered iron stores. RT-PCR was performed using HFE specific primers and duodenal RNA obtained from patients with hemochromatosis, iron deficiency, secondary iron overload and normal controls. The reaction products were visualized by Southern blot and identified by DNA sequence analysis. Additional studies were performed on RNA isolated from liver and a range of human tissues. A truncated (soluble) form of HFE protein was identified that lacks the transmembrane domain and occurs as a result of alternative splicing. Soluble HFE was found predominantly in the duodenum, spleen, breast, skin and testicle. In hereditary hemochromatosis full length HFE was the predominant isoform present in the duodenum similar to iron deficiency. Alternate splicing produces soluble HFE that may have a unique function to regulate cellular iron transport.
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PMID:Alternate splicing produces a soluble form of the hereditary hemochromatosis protein HFE. 1034 14

Iron is required for cellular life. However, abnormalities of its metabolism may lead to iron deficiency or iron overload, both conditions which are deleterious. Therefore, stock and distribution of iron in the body must be very stable. Classically, four major proteins are involved in iron metabolism: (a) transferrin which is implicated in its plasmatic transport, (b) transferrin receptor which regulates iron-transferrin uptake, (c) ferritin, the major iron storage protein, and (d) IRP (Iron Regulatory Protein) which regulates both the entry and storage of iron by linking to the IRE (Iron Responsive Element), a nucleotidic sequence found on transferrin receptor and ferritin mRNA. Thus, IRP adapts gene expression to the iron cellular status. Recent data give informations about new proteins involved in iron metabolism: HFE whose gene is mutated in genetic hemochromatosis, ceruloplasmin which permits cellular iron egress and frataxin which is implicated in the exit of iron from mitochondria.
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PMID:[Current data on iron metabolism]. 1052 Apr 10

The iron content of the body is normally closely regulated. Despite this, iron deficiency anaemia is common in women because iron losses due to menstruation and childbirth are not always compensated for by iron absorption from the diet. The role of transferrin in delivering iron to cells and of ferritin in storing iron within cells is well understood but the proteins involved in iron transport across membranes are only now being investigated. Relatively few genetic disorders affecting iron metabolism are known and most are rare. This paper briefly describes pyridoxine responsive sideroblastic anaemia, hyperferritinaemia-cataract syndrome, atransferrinaemia and genetic haemochromatosis. Rather than rare, the latter is one of the most common inherited disorders in northern European populations. Mutations in genes regulating membrane iron transport causing simple iron deficiency have not yet been described.
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PMID:Inborn errors of metabolism: iron. 1074 46

In 1996 two mutations in Hfe, the gene affected in hereditary hemochromatosis, were identified as C282Y (c.845G. A) and H63D (c.187C. G). Immunohistochemical studies have localized the protein product of Hfe to the deep crypts of the duodenum, the maximum site of iron absorption. To date, there are no published data on the cellular location and regulation of Hfe in patients with hemochromatosis who are homozygous for C282Y. The aim of this study was to identify the cellular localization of Hfe in genotyped individuals and to study possible regulation of this protein by the mutations described in the Hfe gene locus and iron deficiency. Duodenal biopsy specimens and serum for iron, ferritin, and transferrin saturation were taken from controls (n = 10) and patients with hereditary hemochromatosis (n = 10) and iron deficiency anemia (n = 10). All participants were genotyped for C282Y and H63D mutations. Expression of Hfe in the duodenum was demonstrated by immunohistochemistry. Hfe was expressed in the deep crypts of the duodenum in all three groups in a perinuclear fashion. Hfe staining was weaker in the hemochromatosis and iron deficiency patients (mean transferrin saturation 69.6%, SD 23% and 15%, SD 11%, respectively) when compared to controls (mean transferrin saturation 33.1%, SD 15%). There was no difference in the intensity of Hfe staining within the hemochromatosis group who were iron overloaded when compared to their iron-depleted counterparts. In summary, Hfe is expressed strongly in the deep crypts of the small intestine of normal subjects. Homozygosity for C282Y and conditions of iron deficiency result in a downregulation of Hfe. Furthermore, Hfe is not regulated by therapeutic iron depletion in patients with hemochromatosis who are homozygous for the C282Y mutation.
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PMID:Immunohistochemistry of the Hfe protein in patients with hereditary hemochromatosis, iron deficiency anemia, and normal controls. 1077 70

Serum transferrin receptor is considered as a reliable marker of iron status particularly when iron deficiency is associated with chronic disorders such as inflammation, infection or malignancy. The present study aims to illustrate the performances of a new fully automated assay using immunonephelometry. The intra and between-assay precision was found to be very good (CVs < 4%). In healthy subjects there was no statistically significant difference between men and women. With a cut-off of 1.76 mg/l for diagnosing iron deficiency either alone or combined with anemia of chronic diseases, the sensitivity and specificity were respectively 82% and 96.8%. Unlike conventional biochemical and hematological tests, soluble transferrin receptor was unaffected by confounding pathologies. In genetic hemochromatosis the concentration of soluble transferrin receptor was mostly decreased due to the regulatory effect of iron intracellular level. Our study confirms the reliability of soluble transferrin receptor for the assessment of iron status. It is now possible to assay soluble transferrin receptor, ferritin and transferrin on the same apparatus within 15 minutes.
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PMID:Assessment of iron status with a new fully automated assay for transferrin receptor in human serum. 1095 28

The mechanism that leads to iron overload in hereditary hemochromatosis is not yet fully understood and genes other than HFE may be involved. Nramp2 is an intestinal iron transporter, upregulated by dietary iron deficiency, which also colocalizes with transferrin in recycling endosomes. The purpose of the present study was to analyze the coding region of the Nramp2 gene in 14 hemochromatosis probands which did not carry any HFE mutations on both chromosomes. We confirmed the existence of a polymorphism (1254 T --> C), which presumably is not associated with hereditary hemochromatosis, but we did not find any mutation. On the other hand, we identified 17 splice variants of the Nramp2 mRNA. Eight corresponded to activation of cryptic splicing sequences between exons 3 and 4. They were observed in a majority of hemochromatosis probands and control subjects. This indicates the existence of an important splicing instability in this region. At this stage, the biological significance of these variants is unclear. Our study did not find evidence for the involvement of the Nramp2 gene in hereditary hemochromatosis. The remaining question is whether hemochromatosis probands in our study have iron overload because of environmental factors or due to mutation in gene(s) other than HFE and Nramp2.
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PMID:Nramp2 analysis in hemochromatosis probands. 1104 33

We describe a case of homozygosity due to the substitution of aspartic acid with histidine at position 63 of the protein encoded by the gene (known as HFE) associated with hereditary hemochromatosis. Liver biopsy did not disclose stainable iron accumulation; serum ferritin was elevated (639 ng/mL), while the transferrin saturation index was within the normal range (38.1%). As the patient was affected by chronic hepatitis C virus, the high serum ferritin could be attributed to this disease, a frequent occurrence. We also describe a case of heterozygosity for both the substitution of tyrosine with cysteine at position 282 and the substitution of histidine to aspartic acid at position 63 (so-called "compound heterozygosity"). The patient had the typical biochemical abnormalities of iron overload: transferrin saturation index of 53.1% and elevated serum ferritin (658 ng/mL). The removal of > 5 g of iron by phlebotomies did not precipitate iron deficiency. Although the patient refused to undergo liver biopsy, clinical evidence alone enabled a diagnosis of hemochromatosis. These two cases concord with the present scientific orientation, i.e.: 1) homozygosity for the major mutation is associated with the phenotypical (clinical) picture of hemochromatosis, but compound heterozygosity also determines significant iron metabolism abnormalities; 2) homozygosity for the minor mutation does not appear to determine important phenotypical abnormalities.
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PMID:[Significance of "minor" genetic mutations in hereditary hemochromatosis: 2 case reports]. 1105 64

Thirteen adults (eight men, five women) with hemochromatosis had undergone routine iron depletion therapy but while on maintenance phlebotomies developed iron deficiency which persisted for 25 +/- 13 (mean +/- 1 SD) months before diagnosis. All had symptoms and signs of iron deficiency. Levels of transferrin saturation were 10% +/- 5% (1 SD), and serum ferritin concentrations were 8 +/- 3 ng/mL. Eleven had anemia; eight had hypochromia and microcytosis. Bone marrow specimens obtained in five patients revealed no stainable iron. Medical records indicated that parameters of body iron status were infrequently or incorrectly used for adjusting the frequency of phlebotomies. Two patients developed iron deficiency due to additional blood loss from esophageal varices and bilateral hip replacement, respectively. Ten of the patients were treated with ferrous sulfate, 325 mg daily, for 2-6 weeks when anemia was corrected. In patients who were not given iron, anemia and microcytosis recovered in 8-24 months. We conclude that (i) sustained iron deficiency in hemochromatosis patients should be prevented by monitoring hemoglobin levels and serum ferritin; and (ii) hemoglobin concentrations and values of mean corpuscular hemoglobin may be higher in iron-deficient persons with hemochromatosis than in individuals without hemochromatosis. Symptomatic iron deficiency in hemochromatosis patients may be treated safely with a brief course of ferrous sulfate. Recovery is slower when iron is not given. However, iron supplementation is unnecessary and not recommended for the mild, self-limited anemia and decreased serum iron and ferritin concentrations encountered after initial iron depletion therapy for hemochromatosis.
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PMID:Iron deficiency due to excessive therapeutic phlebotomy in hemochromatosis. 1107 39

Iron overload is highly prevalent, but its molecular pathogenesis is poorly understood. Recently, DMT1 was shown to be a major apical iron transporter in absorptive cells of the duodenum. In vivo, it is the only transporter known to be important for the uptake of dietary non-heme iron from the gut lumen. The expression and subcellular localization of DMT1 protein in 3 mouse models of iron overload were examined: hypotransferrinemic (Trf(hpx)) mice, Hfe knockout mice, and B2m knockout mice. Interestingly, in Trf(hpx) homozygotes, DMT1 expression was strongly induced in the villus brush border when compared to control animals. This suggests that DMT1 expression is increased in response to iron deficiency in the erythron, even in the setting of systemic iron overload. In contrast, no increase was seen in DMT1 expression in animals with iron overload resembling human hemochromatosis. Therefore, it does not appear that changes in DMT1 levels are primarily responsible for iron loading in hemochromatosis.
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PMID:Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders. 1115 49


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