A point mutation in the bulge of the iron-responsive element of the L ferritin gene in two families with the hereditary hyperferritinemia-cataract syndrome

The molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome is the presence of a mutation in the iron-responsive element (IRE) of the L ferritin gene, located on chromosome 19q13.3-13.4. Two mutations have been reported so far, altering adjacent nucleotides in the IRE loop, in a region that has been extensively studied in vitro and shown to mediate high affinity interaction with the iron-responsive protein. In this report, we describe two families with a new mutation in the bulge of the IRE stem, and we show that this mutation alters the protein-binding affinity of the IRE in vitro to the same extent as the loop mutation. In addition, we present evidence that some variability in the age of onset of cataract can be associated with this genetic syndrome, probably because of additional genetic or environmental factors that modulate the penetrance of the L ferritin defect in the lens. We confirm that the patients do not have increased iron stores despite the persistence of elevated serum ferritin levels and that, accordingly, they do not tolerate well venesection therapy. Further studies will be necessary to elucidate the mechanism responsible for the onset of cataract.     

Long-term survival of 2 cases of hemochromatosis respectively homozygous for His63Asp and Cys282Tyr mutations]

A 45-year-old Greek patient was found to have a moderate iron overload (ferritin 1213 micrograms/l, serum iron 21.5 mumol/l, transferrin saturation 40%). He underwent 12 phlebotomies of 450 cc over an 8-year period and ferritin was normalized (267 micrograms/l) after the seventh. Study of the HLA-H gene in leukocyte DNA showed that the patient is homozygous for the His63Asp mutation while no modification was found at position 282. This case is compared with that of a 50-year-old Swiss male presenting a severe iron overload (ferritin 7660 micrograms/l, serum iron 36.5 mumol/l, transferrin saturation 97%). Although this patient has undergone 77 phlebotomies (450 cc each time) over a 2-year period, he continues to have a high ferritin level (2200 micrograms/l). HLA-H gene analysis showed the absence of codon 63 mutation and the presence of Cys282Tyr mutation in the homozygous state. The study of these two cases indicates that penetrance of the His63Asp mutation in the homozygous state is very low as compared to Cys282Tyr and results in moderate iron accumulation, probably without organ damage. This genotype must be looked for whenever moderate iron overload is present.     

The effect of interferon and desferrioxamine on serum ferritin and hepatic iron concentrations in chronic hepatitis B

BACKGROUND/AIMS: Recent reports indicate that an individual's iron status might affect the response rate achieved with Interferon therapy for the treatment of chronic viral hepatitis. METHODOLOGY: Forty individuals, 29 men and 11 women, with chronic viral hepatitis B, who had elevated serum ferritin levels, were randomized to receive either Interferon (IFN) 5 MU TIW SQ for 6 months alone (n=21) or Interferon in combination with repetitive cycles of desferrioxamine infused at a dose of 80 mg/kg per cycle (n=19) over 3 consecutive days in an effort to reduce their metabolically active iron pool during the course of IFN treatment. These cycles were continued until a serum ferritin level of less than 250 ng/ml (normal values <220 ng/ml) was achieved. Additionally, all desferrioxamine treated subjects were placed on a low iron containing diet. An interferon response was defined as normalization of the serum ALT and seroconversion from eAg positive to eAb positive. All other responses were defined as failures. RESULTS: The mean ages of the subjects in the 2 groups were 39+/-6 and 38+/-5 years. The initial serum ALT levels were 150+/-27 and 151+/-13 IU/l. The hepatic iron concentrations were 916+/-29 and 896+/-15 microg/g/dry liver weight. The serum ferritin levels were 386+/-12 and 393+/-18 ng/ml. None of these values differed significantly between the 2 treatment groups. The desferrioxamine treated group consisted of 14 men and 5 women. This group experienced a reduction in their serum ferritin to a level of 237+/-13 ng/ml as a result of the desferrioxamine treatment (p<0.05). Additionally, a reduction in their hepatic iron concentration, to a level 766+/-29 microg/g/dry liver weight, occurred with treatment (p<0.05). Twelve of the 19 (63%) desferrioxamine-treated subjects and 8 of the 21 (38%) control subjects experienced a normalization of their serum ALT levels with treatment (p<0.05). Thirteen of 19 (68%) of the desferrioxamine-treated subjects but only 8 of 21 (38%) of the IFN alone treated group seroconverted to anti-e positive (p<0.05). Moreover, a greater improvement in the hepatic histologic score and rate of HBV-DNA loss occurred in the desferrioxamine-treated group. CONCLUSIONS: Based upon these data, it can be concluded that desferrioxamine infusion to achieve a normal serum ferritin level enhances the likelihood of an individual with chronic hepatitis B responding to IFN therapy. The precise mechanism responsible for this phenomenon is not clear, but would appear to be due to a reduction in the hepatic free iron pool as reflected by sequential changes in the serum ferritin and hepatic iron concentrations.     

Ferritin in cultured human cytotrophoblasts: synthesis and subunit distribution

The present study aims at the role of ferritin in the regulation of syncytiotrophoblast free iron levels. The differentiated cytotrophoblast cell in culture is used as a model for this maternal-fetal interface. Cytotrophoblast cells isolated from term placentae are cultured in iron-poor (Medium 199), iron-depleted [desferrioxamine(DFO)] and iron-supplemented [diferric transferrin (hTF-2Fe), ferric ammonium citrate (FAC)] medium. Distribution and de novo synthesis of isoferritins is studied, together with the cellular iron concentration and the ferritin iron saturation. Compared to ferritin isolated from total placenta, ferritin obtained from villous tissue is enriched with acidic isoforms. This observation is in agreement with measured light (L) to heavy (H) subunit ratios < 1 of de novo synthesized ferritin in cultured cytotrophoblast cells. Neither iron-poor culture medium, nor hTf-2Fe supplemented medium affects the cellular iron or ferritin concentration. FAC increased the cellular ferritin iron saturation and (by synthesis) the acidic isoferritin concentrations. The results strongly suggest, that the term syncytiotrophoblast is able to balance transferrin-mediated iron uptake and iron release. In case of FAC supplementation, the syncytiotrophoblast is unable to keep intracellular iron low, and ferritin synthesis is stimulated. The predominance of acidic ferritins and the preferential synthesis of H subunits can be functionally explained by the established fact that iron incorporation in acidic ferritins is faster due to the presence of ferroxidase centres. Damage by free iron catalysed hydroxyl radical formation is therefore minimized.     

Iron balance in hemodialysis patients

Iron deficiency is a frequent complication in chronically hemodialyzed patients because of the significant blood losses associated with this technique. Quantitating iron stores (by marrow examination or serum iron and total iron-binding capacity) on a repetitive basis had been difficult or unreliable, often resulting in failure to recognize iron deficiency superimposed on the existing anemia of chronic renal failure, or overtreating, which can lead to iron excess. Use of the serum ferritin allows easier quantitation of iron stores and, when measured serially in dialysis patients, can predict the emergence of iron deficiency. There was no correlation between serum ferritin levels and serum iron, total iron-binding capacity, or percent transferrin saturation. Iron absorption studies show that food iron absorption is physiologic, increasing when the serum ferritin is below 30 ng/ml, decreasing when more than 300 ng/ml. Treatment of iron deficiency with oral iron compounds increases serum ferritin levels and usually can maintain iron balance.     

Right to left differences in the ankle joint complex range of motion

In most eukaryotic cells, synthesis of the iron storage protein, ferritin is regulated by iron levels and redox conditions. Proper iron storage is important to protect against damaging iron-catalysed free radical reactions. Although iron-catalysed reactions are believed to contribute to oxidative damage and cataractogenesis, little is known about iron storage in the lens. In this study, ferritin concentration was measured in cultured canine lens epithelial cells. Baseline ferritin concentration ranged from 76-163 ng (mg protein)-1; cells cultured in low-iron media had significantly lower ferritin levels than cells cultured in iron-supplemented media. Addition of a large excess of iron as hemin resulted in an eight-fold increase in ferritin concentration. The iron chelator, Desferal, significantly decreased ferritin concentration. The reducing agent dithiothreitol decreased the hemin-induced increase in ferritin levels, but not baseline levels. In contrast, ascorbic acid induced a large increase in ferritin content. Other studies have shown that induction of ferritin synthesis can protect against oxidative damage. Regulation of ferritin levels may represent a mechanism by which the lens epithelium is protected from oxidative damage. In vivo, epithelial cells are normally exposed to much lower iron concentrations than the cultured lens epithelial cells in this study. However, in pathological circumstances, the iron content and redox state of the aqueous humor is dramatically altered and may affect the steady state levels of ferritin within the lens. This remains to be determined.     

The significance of haemochromatosis gene mutations in the general population: implications for screening

BACKGROUND: Haemochromatosis is associated with mutations in the HFE gene but the significance of these mutations in the general population is unknown. AIMS: To determine the frequency of HFE gene mutations in the general population, their effect on serum iron indexes, and their role in screening for haemochromatosis. METHODS: Deoxyribonucleic acid (DNA) from 1064 randomly selected subjects was analysed for the C282Y and H63D mutations in the HFE gene. Serum iron, transferrin saturation, and ferritin were measured and individuals with increased iron indexes were investigated to confirm or exclude a clinical diagnosis of haemochromatosis. RESULTS: Mutations were identified in 409 individuals (38.4%) with heterozygote (carrier) frequencies of 13.2% and 24.3% for the C282Y and H63D mutations respectively. Heterozygosity for either mutation significantly increased serum iron and transferrin saturation but despite a similar trend for ferritin, this was only significant for C282Y homozygotes. Five individuals (0.47%) were homozygous for the C282Y mutation, three of whom had haemochromatosis confirmed by liver biopsy (0.28%). The other two C282Y homozygotes would not have been detected by phenotypic screening alone. CONCLUSIONS: HFE mutations are present in 38.4% of the population, affect serum iron indexes, and are important determinants of iron status. The population frequency of genetically defined haemochromatosis (C282Y homozygosity) is approximately one in 200 and is higher than the prevalence of clinically apparent haemochromatosis.     

Regulation of iron metabolism in the acute-phase response: interferon gamma and tumour necrosis factor alpha induce hypoferraemia, ferritin production and a decrease in circulating transferrin receptors in cancer patients

BACKGROUND: The acute-phase response and anaemia of chronic disease are characterized by hypoferraemia associated with an increased ferritin synthesis, which might be mediated by the activated cytokine cascade. METHODS: We examined the prolonged effects of isolated limb perfusion (ILP) with recombinant human tumour necrosis factor alpha (rTNF), recombinant human interferon gamma (rIFN-gamma) and melphalan on interleukin (IL) 6 and acute-phase protein levels, iron status and serum transferrin receptor (sTfR) levels in 12 patients with melanoma or sarcoma. Patients were treated with ILP during 90 min after pretreatment with rIFN-gamma during 2 days. RESULTS: After ILP, leakage of TNF resulted in systemic peak levels at 3 min followed by an increase in IL-6 with maximum levels at 4h. C-reactive protein (CRP) rose at 4 h to peak levels at day 2, whereas alpha 1-antitrypsin and alpha 1-acid glycoprotein increased to maximum levels at day 3. Albumin and transferrin levels decreased after ILP and recovered after day 2. Serum iron and sTfR levels decreased during pretreatment and after ILP to minimum levels at 8 h and day 1 respectively. This was associated with an increase in serum ferritin levels, which paralleled CRP values. CONCLUSIONS: Our data point to a central role for the cytokine network in the modulation of iron metabolism in the acute-phase response and anaemia of chronic disease. TNF, possibly via induction of IL-6, and IFN-gamma induce hypoferraemia, which may in part result from a decrease in tissue iron release based on a primary stimulation of ferritin synthesis. The fall in sTfR levels may reflect an impaired erythroid growth and/or TfR expression mediated by TNF and IFN-gamma.     

Multicenter study of penile cancer

The objective was to examine the relationships between serum ferritin, alcohol intake, and socioeconomic factors (school education, occupational education, occupation, income, marital status, cohabitation status, housing, social class) in a population survey performed in Copenhagen County during 1982-1984. The participants were selected at random from the census register and comprised 2235 healthy Danish individuals, non-blood donors (1044 men, 1191 women) in cohorts being 30, 40, 50, and 60 years old. The participants gave a detailed social and medical history and had a clinical examination including blood samples. In all age-groups, men had significantly higher serum ferritin and alcohol intake than women. In men, there was no relationship between serum ferritin and social class. Significant relationships were observed between ferritin and occupation (unemployed and self-employed men had higher ferritin than those with other occupations) and ferritin and income (in younger men, ferritin displayed a steady increase with income). None of the social variables were related to the prevalence of iron deficiency or iron overload. Alcohol intake was related to occupation and income, but not to social class. In women, none of the social variables showed any significant relationship to ferritin levels or iron overload. The prevalence of small iron stores (serum ferritin < or = 30 micrograms/l) was lower and the intake of alcohol was higher in women from high social classes. In both men and women, serum ferritin displayed highly significant positive correlations with alcohol intake. Likewise, the prevalence of iron overload (serum ferritin > 90th percentile) was closely correlated to alcohol intake. In conclusion, socioeconomic factors per se had a minor influence on serum ferritin levels and iron status in Danes. The distinct association between alcohol intake and serum ferritin levels should be considered in future iron status surveys.     

Sex differences in the relation of visceral adipose tissue accumulation to total body fatness

With a newly developed short term enzyme linked immunosorbent assay kit (TOYOBO Co.), in which 2 kinds of anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from patients with renal failure and hematological disorders. In this report, the EPO data were analysed in relation to serum iron concentrations, with ferritin and UIBC. In the patients with renal failure, there was no significant correlation between EPO concentration and serum iron, ferritin, nor UIBC concentration. On the other hand, in the patients with hematological disorders, there were two types. One was in patients with iron deficiency anemia, whose serum EPO was negatively correlated to serum iron (r = -0.64) and ferritin (r = -0.59), but positively related to UIBC (r = 0.27). The another was the pattern in patients with aplastic anemia, leukemia and MDS, whose serum EPO positively correlated to iron and ferritin but negatively correlated to UIBC. In the patients with aplastic anemia serum EPO had good correlation to serum iron (r = 0.62), ferritin (r = 0.60) and UIBC (r = -0.46). The relationship of EPO to iron in the patients with leukemia (r = 0.54), and EPO to ferritin in the patients with MDS (r = 0.42) show significantly positive correlation coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multifactor evaluation of the determinants of ischemic electrocardiographic response to maximal treadmill testing in coronary disease

Peripheral blood lymphocytes from patients with all stages of untreated Hodgkin's disease and from normal healthy adults were shown to synthesize and release ferritin in vitro. Ferritin synthesis was confirmed by immunoelectrophoresis, double immunodiffusion and autoradiography. Hodgkin's disease lymphocytes synthesized ferritin 4.2 times faster and released it 2.4 times faster than did normal lymphocytes, whereas total protein synthesis was faster in normal lymphocytes. Patients with nodular sclerosis and perhaps those with absence of fever had the highest synthetic rates; however no relationship was observed between relative rates of lymphocyte ferritin synthesis and sex, age, anatomical stage and presence of splenic or hepatic involvement by tumor. Addition of iron to normal human lymphocytes produced little or no change in ferritin synthesis. These data indicate that part of the intracellular ferritin detected in peripheral blood lymphocytes from patients with Hodgkin's disease and from normal individuals resulted from de novo synthesis rather than from uptake and storage of serum ferritin, and suggests that elevated ferritin levels detected in the serum and tumor tissue of Hodgkin's disease patients originate from lymphocytes.     

Effects of calcium supplementation and lactation on iron status

Calcium has been shown to inhibit iron absorption. The consequences of chronic calcium supplementation on iron status are unclear, however. As part of a randomized calcium-supplementation trial in lactating and nonlactating women in the postpartum period, we determined whether long-term calcium supplementation and lactation status affected iron stores as measured by serum ferritin concentrations. Subjects (95 lactating and 92 nonlactating) were enrolled at approximately 6 mo postpartum and then randomly assigned to receive either 500 mg Ca as calcium carbonate or a placebo twice daily with meals for 6 mo. Lactating women weaned their infants approximately 2 mo after enrollment (ie, approximately 8 mo postpartum). Calcium supplementation had no effect on serum ferritin concentrations. At the end of the study, geometric mean serum ferritin concentrations were 28.4 microg/L in the calcium-supplemented group and 27.5 microg/L in the placebo group (P > 0.5). Lactation status was significantly related to serum ferritin concentrations. At baseline, serum ferritin concentrations were higher in lactating women than in nonlactating women (47.7 compared with 31.5 microg/L, P < 0.001). In lactating women, serum ferritin concentrations decreased by a mean of 17 microg/L after weaning. By 12 mo postpartum, mean serum ferritin concentrations in women who were previously lactating were not significantly higher than those of nonlactating women (30.5 compared with 25.5 microg/L). These findings provide reassurance that long-term calcium supplementation does not impair iron stores. Furthermore, lactation status should be considered when assessing iron nutriture of women and determinants of iron status in populations.     

Analysis of immunoglobulin-synthesizing cells in human dental periapical lesions by in situ hybridization and immunohistochemistry

The iron status of 22 children and adolescents with Crohn's disease (mean age: 13 years) was evaluated. Eleven patients were suffering from active disease with inflammation, identified by at least one abnormal value for serum orosomucoid, C-reactive protein or sedimentation rate (group I). Eleven patients were in clinical remission and showed no biological evidence of inflammation (group II). Hemoglobin and red cell indices, erythrocyte protoporphyrin, serum iron, transferrin, serum ferritin and basic red cell ferritin were determined in all patients. The usual indicators of iron status, particularly serum ferritin, were affected by the inflammatory processes, but basic red cell ferritin appeared to be independent of inflammation. Basic red cell ferritin can therefore be considered to be a reliable indicator of iron status in children and adolescents with Crohn's disease.     

Prognostic significance of febrile episodes in lung cancer patients receiving chemotherapy

AIM: To evaluate the prevalence of iron overload in chronic hepatitis C and its relationship with liver histology. PATIENTS AND METHODS: Serum iron, unsaturated iron binding capacity and ferritin levels were determined in 204 consecutive anti-hepatitis C virus positive subjects, whereas hepatic iron concentration, hepatic histological grading and staging, hepatitis C virus genotypes were further assessed in a subgroup of 50 patients who underwent liver biopsy for chronic hepatitis. RESULTS: An increase in the serum markers of iron metabolism was more frequently found in subjects with aminotransferase activities above the normal range, whereas hepatic iron overload, established by direct hepatic iron determination, was found only in 9/50 (18%) patients with chronic hepatitis C. No serum iron marker could reliably predict hepatic iron stores. Patients with mild iron overload usually showed active hepatitis and fibrosis, whereas iron overload was not present in patients without fibrosis or with very mild fibrosis. Two out of nine patients with iron overload were shown to be beta thalassaemia heterozygous, and two were heterozygous carriers of a putative haemochromatosis gene mutation (His63Asp). CONCLUSIONS: Many anti-hepatitis C virus positive patients with elevated aminotransferase activities have serum ferritin levels above the normal range, but only a minority of patients with chronic hepatitis C have a mild iron overload. In chronic hepatitis C, a relationship does exist between hepatic iron content and liver fibrosis.     

Iron status, menarche, and calcium supplementation in adolescent girls

The effects of growth, menstrual status, and calcium supplementation on iron status were studied over 4 y in 354 girls in pubertal stage 2 who were premenarcheal at baseline (x+/-SD age: 10.8+/-0.8 y). Girls were randomly assigned to placebo or treatment with 1000 mg Ca/d as calcium citrate malate. Anthropometric characteristics, bone mass, and nutritional status were measured biannually; ferritin was measured annually; and red blood cell indexes were determined at 4 y. The simultaneous effects of iron intake and menstrual status on serum ferritin, after change in lean body mass (LBM) was controlled for, were evaluated in subjects in the upper and lower quartiles of cumulative iron intake. The average maximal accumulation of LBM (386 g/mo; 95% CI: 372, 399) occurred 0.5 y before the onset of menarche. Change in LBM was a significant predictor of serum ferritin (P < 0.0001), with a negative influence on iron status (t ratio=-4.12). The 2 fitted mathematical models representing ferritin concentrations of subjects in the upper and lower quartiles of cumulative iron intake were significantly different (P < 0.018). The regression line of the ferritin concentration in menstruating girls with high iron intakes had a less negative slope than the line fit to serum ferritin concentrations in girls with low iron intakes (NS). Serum ferritin concentrations at 0, 1, 2, 3, and 4 y were not significantly different between groups. In addition, there was no significant difference between groups in any of the red blood cell indexes. In summary, growth spurt and menstrual status had adverse effects on iron stores in adolescent girls with low iron intakes (<9 mg/d), whereas long-term supplementation with calcium (total intake: approximately 1500 mg/d) did not affect iron status.     

Changes in biochemical indicators of iron status during iron repletion and depletion in monkeys

Different modes of iron depletion and repletion were studied in monkeys to understand the sequential changes in and the relative importance of different biochemical indicators of iron status. Six control monkeys were divided into two groups, one was fed an iron-deficient diet (group 1) and the other underwent phlebotomy in addition to receiving an iron-deficient diet (group 2). Previously iron-depleted monkeys were subdivided into 4 groups of 3 animals each. While one group was continued on the iron-deficient diet (group 3), the second group received parenteral iron (group 4), the third group (group 5) received a sufficient-iron-containing diet, and the fourth group was fed 50% of the iron requirement. All indicators of iron status like hemoglobin (Hb), erythrocyte protoporphyrin (EPP), serum transferrin saturation and serum ferritin were monitored periodically, in addition to liver and bone marrow iron. all the indicators except serum ferritin and liver iron showed a decrease in group 2. On the other hand, animals receiving parenteral iron (group 4) showed an increase in all the parameters except serum ferritin. The dietary supplementation produced an increase in Hb and a decrease in EPP only (groups 5 and 6). There was a significant positive correlation between changes in bone marrow iron and Hb concentration depending on the severity of depletion and repletion. Both serum ferritin and liver iron did not respond to changes in dietary iron. Another parameter which responded to repletion was EPP. Serum ferritin and liver iron did not respond to changes in dietary iron or was not sensitive to subclinical iron deficiency. The results indicate that change in Hb is more sensitive to detect the deficiency of iron. It was also observed that different parameters respond variably under different modes of depletion and repletion.     

Lexical effects and lexical properties associated with National Adult Reading Test (NART) stimuli in healthy young adults and healthy elderly adults

Among patients with hepatic iron overload, the distinction between hereditary hemochromatosis (HH), a common yet treatable genetic disease, and other causes of siderosis remains problematic. The recent discovery of a specific homozygous mutation (C282Y) in a novel major histocompatibility complex class I-like gene (named HLA-H or HFE) in 80% to 100% of well-characterized cases of HH suggests that direct DNA-based mutation analysis may help resolve this dilemma. To assess the clinical utility of direct HLA-H mutation analysis in a typical diagnostic setting, we measured genotypic and phenotypic parameters of iron overload in 37 subjects with biopsy-proven hepatic siderosis (2+ or greater) and in 127 healthy control subjects. The prevalence of C282Y homozygotes was significantly greater in the hepatic siderosis group (32%) than in the control group (0%), confirming the association between this homozygous mutation and hepatic iron overload. In the hepatic siderosis group, C282Y homozygotes had significantly higher hepatic iron and ferritin levels, a significantly lower prevalence of hepatitis C virus or alcoholic liver disease, but no significant difference in the saturation of serum transferrin. Of the 20 subjects with a hepatic iron index (HII) in the previously defined "hemochromatosis range" (>1.9), 9 (45%) were C282Y homozygotes. Of the 11 nonhomozygous subjects with an HII greater than 1.9 (presumed false-positive HIIs), 10 (91%) had hepatic cirrhosis compared with 3 of 9 (33%) homozygotes with an HII greater than 1.9 who had cirrhosis (P<.02). The HII thus has poor diagnostic specificity for predicting genotypic HH in patients with cirrhosis. We conclude that direct determination of the HLA-H C282Y genotype may be the single best diagnostic test for HH, particularly in patients with cirrhosis, for whom the HII is quite nonspecific.     

Serum ferritin as a control parameter for oral iron therapy (author's transl)

Ferrritin can be measured in blood serum radioimmunometrically. Serum ferritin is directly correlated to body iron stores. In comparison to other parameters of storage iron (bone marrow iron, intestinal iron absorption) this quantitative diagnostic parameter is easily available. Thus it can be used to judge body iron status. In 20 patients with chronic haemorrhagic and 7 patients with posthaemorrhagic iron deficiency anaemia as well as nine blood donors with latent iron deficiency serum ferritin was used to control oral iron therapy. The continuous determination of serum ferritin during therapy gives a quantitative value of the relevant level of body iron stores. This value shows whether therapy was effective and when iron stores are replenished. The results demonstrate that oral iron therapy should be continued for at least 3 months from the time of normalisation of haemoglobin to obtain a sufficient restoration of iron depots.