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PubMed2001

Iron overload impairs pro-inflammatory cytokine responses by Kupffer cells.

AIM: The aim of the present study was to determine the effect of chronic iron overload on Kupffer cell cytokine production. METHODS: Kupffer cells were isolated from rats that were fed either a control or iron-supplemented diet for 12 months. Cytokine mRNA and protein levels were determined by using a ribonuclease protection assay and ELISA, respectively. RESULTS: Baseline levels of tumor necrosis factor-alpha, transforming growth factor-beta1, interleukin-6 and granulocyte macrophage colony stimulating factor were similar in iron-loaded and control Kupffer cells. Following the addition of lipopolysaccharide to control cells, tumor necrosis factor-alpha, interleukin-1alpha and interleukin-6 mRNA levels increased. Tumor necrosis factor-alpha mRNA and protein levels were reduced by 40 and 60%, respectively, in iron-loaded cells compared with controls following the addition of lipopolysaccharide. Interleukin-6 mRNA levels in iron-loaded Kupffer cells were also reduced. Granulocyte macrophage colony stimulating factor mRNA levels remained unchanged in controls, but were significantly elevated in iron-loaded cells. Tumor growth factor-beta1 mRNA and protein levels were similar in control and iron-loaded cells. CONCLUSION: Deposition of iron in Kupffer cells in chronic dietary iron overload results in an impaired pro-inflammatory cytokine response to lipopolysaccharide. Our observations may have relevance to the altered immune function observed in chronic iron-overload syndromes.

Animals↗
PubMed1981

Clinical consequences of acquired transfusional iron overload in adults.

We assessed the clinical sequelae of transfusional iron overload in 15 nonthalassemic adults (40 to 71 years of age) with anemias requiring transfusions. Iron loading had been present for less than four years in 14 patients. The number of units of blood transfused ranged from 60 to 210 (mean, 120). Liver-biopsy specimens in 10 patients contained seven to 26 times the normal amount of iron and typically showed focal portal fibrosis. Left ventricular cardiac function was impaired in only the most heavily transfused patients or in those with coexisting coronary-artery disease, All patients had glucose intolerance associated with significantly reduced insulin output, compared with controls (P < 0.01). Pituitary reserve of ACTH was limited in 10 of 12 patients, and that of gonadotropin in five of 13. We conclude that widespread subclinical organ dysfunction can result from transfusional iron overload developing in adulthood. The pattern of organ involvement resembles that encountered in idiopathic hemochromatosis.

Adult↗
PubMedDate not supplied

Molecular analysis of iron overload in beta2-microglobulin-deficient mice.

Beta2-microglobulin knockout (beta2m-/-) mice represent an instructive model of spontaneous iron overload resembling genetic hemochromatosis. The mechanism of iron accumulation in this mouse model may be more complex than involving the MHC class I-like protein HFE. We report that beta2m-deficient mice, like Hfe-/- mice, lack the adaptive hepatic hepcidin mRNA increase to iron overload. The inverse correlation of hepatic iron levels and hepcidin mRNA expression in six beta2m-/- mice underlines the importance of hepcidin in regulating body iron stores. In contrast to Hfe-/- mice, beta2m-deficient mice display increased expression of the duodenal iron transporters DMT1 and ferroportin 1. This result implicates a broader role of beta2m in mammalian iron metabolism, suggesting that (an) additional beta2m-interacting protein(s) could be involved in controlling iron homeostasis, and highlighting the emerging connection of iron metabolism with the immune system.

Animals↗
PubMed1995

A long-term study of the interaction between iron and alcohol in an animal model of iron overload.

BACKGROUND/AIMS: The hypothesis that chronic alcohol ingestion potentiates iron-associated liver injury was investigated in the 'carbonyl iron-overload rat model'. METHODS: Newborn male and female Wistar-Furth rats (seven per group) were used to investigate iron-alcohol interaction over a 26-week period. Groups 1 and 2 were iron loaded from birth, while the others received normal diet. At 10 weeks all rats commenced Lieber-DeCarli liquid diet; additional treatments were: group 1 6 g carbonyl iron/1000 ml diet plus alcohol; group 2 carbonyl iron in the liquid diet; group 3 alcohol in the liquid diet; group 4, the controls, received liquid diet only. RESULTS: This study confirmed our previous observation that iron-loading from birth resulted in grade III-IV siderosis, in both male and female rats, and caused fibrosis associated with periportal macrophages. Alcohol-feeding, in addition to iron-feeding for 26 weeks significantly lowered the hepatic iron concentration in both male and female rats compared to those fed iron only (p < 0.05). Alcohol feeding did increase hepatic fibrosis in the iron-loaded animals. However, serum alanine aminotransferase activity was significantly higher in the iron-alcohol group than in the other groups (p < 0.05). CONCLUSIONS: Thus, contrary to expectation, chronic alcohol feeding failed to potentiate hepatic fibrosis in iron-overloaded rats, although there was rather more hepatocyte necrosis, and the serum alanine aminotransferase activity was significantly higher in the iron-alcohol group than in the other groups.

Alcoholism↗
PubMed1981

Hepatocellular adenoma in a young woman with beta-thalassemia and secondary iron overload.

The occurrence of a hepatocellular adenoma is described in a young woman with beta-thalassemia and secondary iron overload. This patient had no history of oral contraceptive use, and in fact was hypogonadal as a result of iron deposition in pituitary and gonadal tissue. Although hepatocellular carcinoma frequently occurs in diseases associated with iron overload, this is the first report of a benign liver tumor associated with secondary iron overload.

Adolescent↗
PubMed1995

Iron deficiency and iron overload in Swedish male adolescents.

OBJECTIVES: The present study was undertaken to confirm or reject recent findings indicating a high prevalence of iron deficiency in Swedish male adolescents; a second aim was to study the prevalence of genetic iron overload. DESIGN: The diagnostic criteria were: anaemia: Hb < 130 g L-1 (a): iron deficiency: serum ferritin (SF) < 12 micrograms L-1 + transferrin saturation (TS) < 16% (b): iron deficiency anaemia a + b. Iron overload: SF (90th percentile) + TS (90th percentile) in repeat tests. SETTING: Central Sweden. SUBJECTS: A total 3975 men aged 18 years studied on enrollment into military service. RESULTS: Serum ferritin averaged 36.8 micrograms L-1. Anaemia was present in 0.5%, iron deficiency anaemia in 0.17% and iron deficiency in 0.4%. If iron deficiency is defined as SF < 16 micrograms L-1, as was recently suggested, the prevalence would be 2.8%. Such a cut-off value would include 73% normal people (false positives). Iron overload had the same prevalence as iron deficiency, 0.4%. CONCLUSIONS: Iron stores, as measured by serum ferritin, are small in young men studied at the end of their growth spurt. However, iron deficiency is rare. Therefore, the present study has not been able to confirm the high prevalence of iron deficiency recently reported. A prevalence of genetic haemochromatosis of 0.4%, confirms earlier findings and would mean that 12.6% of the population are heterozygotic carriers of the iron-loading genes. These findings give no support for a proposed, more effective iron-enrichment of food. It is not needed and can be harmful.

Adolescent↗
PubMed1989

Hepatic injury in chronic iron overload. Role of lipid peroxidation.

In both hereditary hemochromatosis and in the various forms of secondary hemochromatosis, there is a pathologic expansion of body iron stores due mainly to an increase in absorption of dietary iron. Excess deposition of iron in the parenchymal tissues of several organs (e.g. liver, heart, pancreas, joints, endocrine glands) results in cell injury and functional insufficiency. In the liver, the major pathological manifestations of chronic iron overload are fibrosis and ultimately cirrhosis. Evidence for hepatotoxicity due to iron has been provided by several clinical studies, however the specific pathophysiologic mechanisms for hepatocellular injury and hepatic fibrosis in chronic iron overload are poorly understood. The postulated mechanisms of liver injury in chronic iron overload include (a) increased lysosomal membrane fragility, perhaps mediated by iron-induced lipid peroxidation, (b) peroxidative damage to mitochondria and microsomes resulting in organelle dysfunction, (c) a direct effect of iron on collagen biosynthesis and (d) a combination of all of the above.

Animals↗
PubMed1990

Dietary iron overload in southern African rural blacks.

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1997

Effect of vitamin E supplementation on hepatic fibrogenesis in chronic dietary iron overload.

It has been suggested that lipid peroxidation plays an important role in hepatic fibrogenesis resulting from chronic iron overload. Vitamin E is an important lipid-soluble antioxidant that has been shown to be decreased in patients with hereditary hemochromatosis and in experimental iron overload. The aim of this study was to determine the effects of vitamin E supplementation on hepatic lipid peroxidation and fibrogenesis in an animal model of chronic iron overload. Rats were fed the following diets for 4, 8, or 14 mo: standard laboratory diet (control), diet with supplemental vitamin E (200 IU/kg, control + E), diet with carbonyl iron (Fe), and diet with carbonyl iron supplemented with vitamin E (200 IU/kg. Fe + E). Iron loading resulted in significant decreases in hepatic and plasma vitamin E levels at all time points, which were overcome by vitamin E supplementation. Thiobarbituric acid-reactive substances (an index of lipid peroxidation) were increased three- to fivefold in the iron-loaded livers; supplementation with vitamin E reduced these levels by at least 50% at all time points. Hepatic hydroxyproline levels were increased twofold by iron loading. Vitamin E did not affect hydroxyproline content at 4 or 8 mo but caused an 18% reduction at 14 mo in iron-loaded livers. At 8 and 14 mo, vitamin E decreased the number of alpha-smooth muscle actin-positive stellate cells in iron-loaded livers. These results demonstrate a dissociation between lipid peroxidation and collagen production and suggest that the profibrogenic action of iron in this model is mediated through effects which cannot be completely suppressed by vitamin E.

Alanine Transaminase↗
PubMed1991

[The value of nuclear magnetic resonance in the study of iron overload in thalassemia patients].

In patients with thalassemia treated by long-term chronic blood transfusions who survive beyond the first ten or twenty years of life but received no or inadequate chelating therapy during the first years, evaluation of iron overload and its consequences on tissues may prove an arduous task. MRI is a non-invasive means of measuring the amount of iron in the liver and the consequences of the iron overload on the heart and other tissues. For this purpose, MRI is more satisfactory than CT scan studies. In this investigation, 20 patients with thalassemia major underwent MRI. Multiple spin echos were used to allow determination of the transversal relaxation constant T2. This constant, expressed in ms, is related to the concentration of iron in the liver as in the following expression: (C) = 5 410/T2-110. MRI studies disclosed a discrepancy between the severity of hepatic hemosiderosis and development of decompensated iron overload cardiomyopathy. In a unique case, in which a heart transplant and two MRI studies were performed, the severe iron overload that failed to respond to several years of subcutaneous chelating therapy was more than halved by intensive intravenous chelation through a central catheter. MRI studies of the heart provide valuable morphologic and functional data. Although the amount of iron in the myocardium cannot as yet be quantified, modifications of the transversal relaxation time provide information on the severity of the overload and the presence of other myocardial alterations.

Adolescent↗
PubMed1997

T lymphocytes subsets in experimental iron overload.

Several abnormalities of the immune system have been reported in association with clinical and experimental iron overload. To dissect further such abnormalities, changes in lymphocyte subsets were evaluated in iron-loaded male Sprague-Dawley rats. The iron-loading protocol consisted of a total dose of irondextran (1.5 mg/Kg body weight) divided in daily intramuscular injections over twenty consecutive days. At days 0, 20, and 50 after initiation of iron injections lymphocyte subsets in blood, spleen and mesenteric lymph nodes were estimated by indirect immunofluorescence using monoclonal antibodies recognizing T cells (W3.13), the subset of helper T cells in (W3.25), and the subset of cytotoxic T cells (OX.8). By day 20, there was no change in the number of W3.25+ T cells in the blood of iron-loaded animals as compared to the controls, but the OX.8+ T cells were significantly elevated. At this time, the ratio W3.25 +/OX.8+ cells was significantly decreased (0.5 in experimental rats vs 2.0 in controls). Similar results were obtained at day 50. In the spleen, there was a decrease in the proportion of W3.25 +T cells and an increase in OX.8+ T cells at day 20. However, these values returned to normal by day 50. A negative correlation between W3.25 +/OX.8+ ratio and serum ferritin was observed in blood and spleen during iron administration. These changes were associated with abnormalities in lymphocyte proliferative response. No changes in W3.25 +/OX.8+ ratio were observed in mesenteric lymph nodes. These results demonstrate that iron overload alters the distribution of T lymphocytes in various compartments of the immune system.

Animals↗
PubMedDate not supplied

Contribution of different HFE genotypes to iron overload disease: a pooled analysis.

PURPOSE: To determine the contribution of the C282Y and H63D mutations in the HFE gene to clinical expression of hereditary hemochromatosis. METHODS: Pooled analysis of 14 case-control studies reporting HFE genotype data, to evaluate the association of different HFE genotypes with iron overload. In addition, we used data from the pooled analysis and published data to estimate the penetrance of the C282Y/C282Y genotype. RESULTS: Homozygosity for the C282Y mutation carried the largest risk for iron overload (OR = 4383, 95% CI 1374 to >10,000) and accounted for the majority of hemochromatosis cases (attributable fraction (AF) = 0.73). Risks for other genotypes were much smaller: OR = 32 for genotype C282Y/H63D (95% CI 18.5 to 55.4, AF = 0.06); OR = 5.7 for H63D/H63D (95% CI 3.2 to 10.1, AF = 0.01); OR = 4.1 for C282Y heterozygosity (95% CI 2.9 to 5.8, with heterogeneity in study results, making this association uncertain); and OR = 1.6 for H63D heterozygosity (95% CI 1 to 2.6, AF = 0.03). Estimates of penetrance for the C282Y/C282Y genotype were highly sensitive to estimates of the prevalence of iron overload disease. At a prevalence of 2.5 per 1000 or less, penetrance of the C282Y/C282Y genotype is unlikely to exceed 50%. Penetrance of other HFE genotypes is much lower. CONCLUSIONS: C282Y homozygosity confers the highest risk for iron overload but the H63D mutation is also associated with increased risk. Our data indicate a gradient of risk associated with different HFE genotypes and thus suggest the presence of other modifiers, either genetic or environmental, that contribute to the clinical expression of hemochromatosis.

Amino Acid Substitution↗
PubMed1993

Metabolism of iron from (3,5,5-trimethylhexanoyl)ferrocene in rats. A dietary model for severe iron overload.

The feeding of diets enriched with (3,5,5-trimethylhexanoyl)ferrocene (TMH-ferrocene) has been shown recently to produce a severe experimental iron overload in rats and has been considered as an adequate animal model for hereditary haemochromatosis in humans. We synthesized three 59Fe-labelled ferrocene compounds with different lipophilic characters (ferrocene, TMH-ferrocene, and 1,1'-bis(3,5,5-trimethylhexanoyl)ferrocene [(TMH)2-ferrocene]) and studied the metabolism of iron from these compounds in comparison with the hydrophilic ferrous sulphate in rats with iron deficiency, and normal and increased iron stores. The bioavailability of iron from TMH-ferrocene (whole body retention, 48% from a 5 mg Fe dose) was twice as high as from ferrocene and six times higher than from (TMH)2-ferrocene and ferrous sulphate. In contrast to the well-known iron salts (ferrous sulphate), the intestinal absorption of TMH-ferrocene iron was independent from the dose (1 or 5 mg Fe) and similar in iron-deficient and iron-loaded rats, indicating that the intestinal absorption of the TMH-ferrocene is not regulated by the body iron stores. After intestinal absorption, TMH-ferrocene iron in the portal blood is transported to the liver independently from transferrin. In contrast to absorbed ferrocene, iron from TMH-ferrocene is almost completely released from the hydrocarbon moiety within the liver. Depending on the body iron stores, TMH-ferrocene iron is then incorporated preferentially into haemoglobin (iron-deficient rats) or added to the iron stores in the liver (iron-loaded rats). A transient storage of the 59Fe-label in fat tissue was observed only from oral ferrocene but not from TMH-ferrocene. Due to the outstandingly high bioavailability of TMH-ferrocene, the chronic feeding of this compound resulted in a fast and progressive iron overload in rats (liver iron: 16.9 mg Fe/g wet weight after 10 weeks of feeding a diet containing 0.5% TMH-ferrocene), and can be regarded as the best characterized and most useful animal model for severe hepatocellular iron overload in humans.

Animals↗
PubMed2005

Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia.

BACKGROUND: Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells. Repeated transfusions results in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. Desferrioxamine is the most widely used iron chelator. Substantial data have shown the beneficial effects of desferrioxamine. However, important questions exist about whether desferrioxamine is the best schedule for iron chelation therapy. OBJECTIVES: To determine the effectiveness (dose and method of administration) of desferrioxamine in people with transfusion-dependent thalassaemia. SEARCH STRATEGY: We searched the Cochrane Haemoglobinopathies Trials Register, MEDLINE, EMBASE, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We also contacted the manufacturers of desferrioxamine and other iron chelators. Date of last searches: April 2004. SELECTION CRITERIA: Randomised controlled trials comparing desferrioxamine with placebo; with another iron chelator; or comparing two schedules of desferrioxamine, in people with transfusion-dependent thalassaemia. DATA COLLECTION AND ANALYSIS: Four authors working independently, were involved in trial quality assessment and data extraction. Missing data were requested from the original investigators. MAIN RESULTS: Eight trials involving 334 people (range 20 to 144 people) were included. One trial compared desferrioxamine with placebo, five compared desferrioxamine with another iron chelator (deferiprone) and two compared different schedules of desferrioxamine. Overall, few trials measured the same outcomes.Compared to placebo, desferrioxamine significantly reduced iron overload. The number of deaths at 12 years follow up and evidence of reduced end-organ damage was less for desferrioxamine than placebo. When desferrioxamine was compared to deferiprone or a different desferrioxamine schedule there were no statistically significant differences in measures of iron overload. Compliance was recorded by two trials. Compliance was less for desferrioxamine than deferiprone in one trial and of no difference in comparison with desferrioxamine and deferiprone combined with a second trial. Adverse events were recorded in trials comparing desferrioxamine with other iron chelators. There was evidence of adverse events in all treatment groups. In one trial, adverse events were significantly less likely with desferrioxamine than deferiprone, relative risk 0.45 (95% confidence interval 0.24 to 0.84). Assessment of the methodological quality of included trials was not possible, given the general absence of these data in the trials. AUTHORS' CONCLUSIONS: We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Chelation Therapy↗
PubMed2001

HFE mutations do not account for transfusional iron overload in patients with acute myeloid leukemia.

BACKGROUND: Hereditary hemochromatosis (HH) is a HFE gene-linked disorder affecting 1 of 200 to 400 persons in white populations. It has been proposed that patients with a hematologic malignancy who are receiving frequent RBC transfusions should be screened for HFE mutations. This would identify C282Y homozygotes, who have a high risk of developing severe iron overload. STUDY DESIGN AND METHODS: DNA samples from 128 controls and 23 adult long-term survivors of acute myeloid leukemia (AML) treated at the Oulu University Hospital (Oulu, Finland) from 1987 to 2000 were examined for the presence of the C282Y and H63D mutations in HFE. All the patients were severely iron-overloaded, as determined from high serum ferritin values and/or increased storage iron in bone marrow. Phlebotomies were performed in five patients because of the symptoms of iron overload. DNA extracted from the blood was used to amplify HFE gene fragments by the PCR method, after which the amplification products were digested with restriction endonucleases SnaB I and Bcl I, and the restriction fragments were analyzed on agarose gels. RESULTS: No chromosomes with the C282Y mutation were found among the AML patients, and 5 patients (21.7%) were heterozygous for the H63D mutation. In the control group, 13 persons (10.2%) were heterozygous for the C282Y mutation and 26 (20.3%) for the H63D mutation, including 3 C282Y/H63D double heterozygotes. CONCLUSION: HFE mutations do not account for the harmful iron overload that develops in AML patients who receive large quantities of RBC concentrates after intensive chemotherapy.

Acute Disease↗
PubMed1999

Deferiprone: a review of its clinical potential in iron overload in beta-thalassaemia major and other transfusion-dependent diseases.

UNLABELLED: Patients with beta-thalassaemia and other transfusion-dependent diseases develop iron overload from chronic blood transfusions and require regular iron chelation to prevent potentially fatal iron-related complications. The only iron chelator currently widely available is deferoxamine, which is expensive and requires prolonged subcutaneous infusion 3 to 7 times per week or daily intramuscular injections. Moreover, some patients are unable to tolerate deferoxamine and compliance with the drug is poor in many patients. Deferiprone is the most extensively studied oral iron chelator to date. Non-comparative clinical studies mostly in patients with beta-thalassaemia have demonstrated that deferiprone 75 to 100 mg/kg/day can reduce iron burden in regularly transfused iron-overloaded patients. Serum ferritin levels are generally reduced in patients with very high pretreatment levels and are frequently maintained within an acceptable range in those who are already adequately chelated. Deferiprone is not effective in all patients (some of whom show increases in serum ferritin and/or liver iron content, particularly during long term therapy). This may reflect factors such as suboptimal dosage and/or severe degree of iron overload at baseline in some instances. Although few long term comparative data are available, deferiprone at the recommended dosage of 75 mg/kg/day appears to be less effective than deferoxamine; however, compliance is superior with deferiprone, which may partly compensate for this. Deferiprone has additive, or possibly synergistic, effects on iron excretion when combined with deferoxamine. The optimum dosage and long term efficacy of deferiprone, and its effects on survival and progression of iron-related organ damage, remain to be established. The most important adverse effects in deferiprone-treated patients are arthropathy and neutropenia/agranulocytosis. Other adverse events include gastrointestinal disturbances, ALT elevation, development of antinuclear antibodies and zinc deficiency. With deferiprone, adverse effects occur mostly in heavily iron-loaded patients, whereas with deferoxamine adverse effects occur predominantly when body iron burden is lower. CONCLUSION: Deferiprone is the most promising oral iron chelator under development at present. Further studies are required to determine the best way to use this new drug. Although it appears to be less effective than deferoxamine at the recommended dosage and there are concerns regarding its tolerability, it may nevertheless offer a therapeutic alternative in the management of patients unable or unwilling to receive the latter drug. Deferipone also shows promise as an adjunct to deferoxamine therapy in patients with insufficient response and may prove useful as a maintenance treatment to interpose between treatments.

Clinical Trials as Topic↗
PubMed1981

Iron overload in beta-thalassaemia minor. A family study.

23 descendents of a 74--year-old Englishman who had beta-thalassaemia trait, and died of hepatoma, were studied to discover whether thalassaemia minor alone could predispose to iron overload. Serum ferritin and HLA antigens were assessed in all members, and adults underwent radioiron investigations and liver biopsy. 2 members of the second generation and 1 of the third generation, all of whom had thalassaemia trait, had elevated liver iron concentration, indicating preclinical iron overload. This was not associated with any HLA type. None of the subjects had been treated with exogenous iron. The one member of the second generation who had thalassaemia minor but not iron overload was female, and the 5 members of the third generation with the trait, but with normal serum ferritin levels, were all under the age of 15 years. Members of the family without beta-thalassaemia minor had normal iron metabolism. It is possible that the development of iron overload in 4 members of this family was related to the presence of thalassaemia minor, and not to the inheritance of another abnormal gene causing idiopathic haemochromatosis.

Adolescent↗