Prediction of the helix/strand content of globular proteins based on their primary sequences

Population screening for hemochromatosis done by using the transferrin saturation test has been advocated by experts to permit the initiation of therapeutic phlebotomy before the onset of clinical disease. The discovery of a gene associated with hemochromatosis has made DNA testing another option for screening and diagnosis. In this paper, U.S. Preventive Services Task Force criteria are used to evaluate the evidence for the usefulness of population screening done by using iron measures or genetic testing. Published clinical research offers little evidence to suggest that population screening for hemochromatosis done by using genetic testing improves clinical outcomes. Although one recently discovered mutation, C282Y, accounts for 60% to 92% of cases of the disease in series of patients with hemochromatosis, uncertainties remain about the clinical penetrance of various genotypes; the accuracy of genetic testing; and the ethical, legal, and social effects of genetic testing. Before population screening for hemochromatosis done by using transferrin saturation testing can be recommended, laboratory standardization needs to be addressed and questions about risk for clinical disease in asymptomatic persons with mutations or early biochemical expression of disease require resolution. Evidence from case series suggests that hemochromatosis may be associated with liver cancer, other liver disease, diabetes, bradyarrhythmias, and arthritis. In all studies but one, however, estimation of the magnitude and significance of this risk is limited by lack of adequate comparison groups. The need for population data to answer questions about penetrance among asymptomatic persons should not impede efforts to increase the detection and treatment of hemochromatosis in persons found to have elevated iron measures a family history of hemochromatosis, or consistent early signs and symptoms of the disease.     

A randomized study of two doses of abdominopelvic radiation therapy for patients with optimally debulked Stage I, II, and III ovarian cancer

BACKGROUND & AIMS: An elevated transferrin saturation is the earliest phenotypic abnormality in hereditary hemochromatosis. Determination of transferrin saturation remains the most useful noninvasive screening test for affected individuals, but there is debate as to the appropriate screening level. The aims of this study were to estimate the mean transferrin saturation in hemochromatosis heterozygotes and normal individuals and to evaluate potential transferrin saturation screening levels. METHODS: Statistical mixture modeling was applied to data from a survey of asymptomatic Australians to estimate the mean transferrin saturation in hemochromatosis heterozygotes and normal individuals. To evaluate potential transferrin saturation screening levels, modeling results were compared with data from identified hemochromatosis heterozygotes and homozygotes. RESULTS: After removal of hemochromatosis homozygotes, two populations of transferrin saturation were identified in asymptomatic Australians (P < 0.01). In men, 88.2% of the truncated sample had a lower mean transferrin saturation of 24.1%, whereas 11.8% had an increased mean transferrin saturation of 37.3%. Similar results were found in women. A transferrin saturation threshold of 45% identified 98% of homozygotes without misidentifying any normal individuals. CONCLUSIONS: The results confirm that hemochromatosis heterozygotes form a distinct transferrin saturation subpopulation and support the use of transferrin saturation as an inexpensive screening test for hemochromatosis. In practice, a fasting transferrin saturation of > or = 45% identifies virtually all affected homozygous subjects without necessitating further investigation of unaffected normal individuals.     

Source of dietary protein influences kinetics of plasma gut regulatory peptide concentration in response to feeding in preruminant calves

Anaemia in pregnancy in developing countries continues to be a public health problem of significant proportion. At least 50% of the anaemia has been blamed on iron deficiency. In populations where chronic inflammation and iron deficiency anaemia coexist, the criteria to accurately define iron status are not always clear. Similarly, in pregnancy, with marked physiological changes, cut-off points for biochemical parameters need to be re-examined. In this study we examined the diagnostic accuracy of iron parameters including mean cellular volume (MCV), serum iron, transferrin, total iron binding capacity (TIBC) and its saturation, zinc protoporphyrin (ZPP), ferritin and serum transferrin receptor (TfR) for the assessment of iron status in a population of anaemic pregnant women in Malawi. Stained bone marrow aspirates were used as the standard for comparison. Results show that for the purpose of screening, serum ferritin is the best single indicator of storage iron provided a cut-off point of 30 microg/l is used. A number of other commonly used parameters of iron status were shown to have limited diagnostic accuracy. Logistic regression was used to obtain mathematical models for the prediction of bone marrow iron status using a combination of available parameters.     

Hereditary hemochromatosis

Genetic (hereditary) hemochromatosis is probably the most common autosomal recessive disorder found in white Americans, of whom about 5/1,000 (0.5 percent) are homozygous for the associated gene. The hemochromatosis gene is probably located close to the HLA-A locus on the short arm of chromosome 6. Homozygous individuals may develop severe and potentially lethal hemochromatosis, especially after age 39. Hereditary hemochromatosis involves an increased rate of iron absorption from the gut with subsequent progressive storage of iron in soft organs of the body. Excess iron storage eventually produces pituitary, pancreatic, cardiac, and liver dysfunction and death may result from cardiac arrhythmias, congestive heart failure, and/or hepatic failure or cancer. Early diagnosis can prevent these excess iron-induced problems. Iron overload owing to HLA-linked hereditary hemochromatosis can be distinguished from other causes of hemochromatosis by liver biopsies and interpretations. Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations. Family members of hereditary hemochromatosis patients are at increased risk and should be tested. Screening, identification and early treatment (phlebotomies, sometimes in combination with the use of Desferal or other iron-chelating agents) may help prevent or reduce iron-related organ damage and premature deaths. Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.     

Hemochromatosis-associated mortality in the United States from 1979 to 1992: an analysis of Multiple-Cause Mortality Data

BACKGROUND: Hemochromatosis, which can lead to serious chronic diseases resulting from iron overload, has an estimated prevalence of 50 to 80 cases per 10000 persons. However, little population-based information is available on the impact of hemochromatosis on morbidity and mortality. OBJECTIVE: To evaluate trends over 14 years in deaths and medical conditions associated with hemochromatosis in the United States. DESIGN: We searched Multiple-Cause Mortality Files compiled by the National Center for Health Statistics for the years 1979 to 1992 for all records listing hemochromatosis. We used these data to calculate age-adjusted and age-specific mortality rates, identify medical conditions associated with a known diagnosis of hemochromatosis at death, and calculate proportionate mortality ratios for these medical conditions. RESULTS: The listing of hemochromatosis on death certificates increased 60% from 1979 to 1992. Decedents with hemochromatosis were 23, 13, and 5 times more likely to have liver neoplasms, liver disease, and cardiomyopathy, respectively, than were decedents without hemochromatosis. Conversely, decedents with liver neoplasms, liver disease, and cardiomyopathy were 26, 14, and 5 times more likely, respectively, to have hemochromatosis than were decedents without these conditions. Hemochromatosis was 82 times more likely in persons with the combination of liver neoplasms and diabetes and 43 times more likely in those with the combination of liver disease and diabetes than in those without these conditions. CONCLUSIONS: Comparison of the reported prevalence of hemochromatosis among decedents with estimates of prevalence in the general U.S. population suggests that either the penetrance or the recognition of hemochromatosis, or both, is low. Nevertheless, substantial mortality resulting from liver disease, liver neoplasms, cardiomyopathy, and a combination of liver disease and diabetes in patients with hemochromatosis argues for the improved diagnosis and treatment of hemochromatosis in persons with these conditions.     

Iron-related indexes in chronic alcoholics. Effect of alcohol withdrawal

BACKGROUND: Increased serum transferrin saturation and ferritin levels have been reported in chronic alcoholics. AIM: To evaluate modifications in serum iron-related indexes in chronic alcohol abusers with and without cirrhosis, at enrolment and after complete alcohol withdrawal. PATIENTS: Fifty-one consecutive chronic alcohol abusers, 33 without and 18 with cirrhosis. METHODS: Liver function tests were performed and transferrin saturation percent and serum ferritin levels measured at time 0 and after 7 and 14 days of complete alcohol withdrawal. RESULTS: Duration of alcohol abuse was significantly longer in patients with cirrhosis than in those without (24 +/- 13 SD vs 18 +/- 13 SD years, p < 0.01). A concomitant increase in transferrin saturation percent and serum ferritin was found in 60% of the cirrhotics and 45% of the non cirrhotic group. During the observation period, transferrin saturation percent and serum ferritin fell significantly in both groups (from 59 +/- 33 SD to 36 +/- 22% SD, p < 0.05, and from 900 +/- 933 SD to 469 +/- 457 SD ng/ml, p < 0.01, in cirrhotics, and from 46 +/- 30 SD to 27 +/- 12% SD, p < 0.01, and from 702 +/- 602 SD to 340 +/- 29 SD ng/ml, p < 0.01, in non cirrhotics). CONCLUSIONS: Iron-related indexes increase with chronic alcohol abuse and return to normal rapidly after complete alcohol withdrawal. In chronic alcoholics the timing of determinations of iron-related indexes is crucial, and screening for possible concomitant genetic haemochromatosis must be postponed.     

Current diagnosis: hereditary metabolic diseases of the liver (primary hemochromatosis, Wilson disease)

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

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.     

'Oversaturation' of transferrin after intravenous ferric gluconate (Ferrlecit(R)) in haemodialysis patients

BACKGROUND: Chronic haemodialysis causes blood loss and iron-deficiency. This can be corrected with intravenous preparations, e.g. sodium ferric-gluconate (FeGl). In two patents complaints of hypotension and malaise during FeGl infusion coincided with high levels of serum iron and a calculated transferrin iron saturation above 100%. Iron toxicity could be the cause of these complaints. Free iron is known to aggravate the toxicity of free radicals and other reactive oxygen products that are constantly formed in the body. We compared four rates of FeGl infusion with regard to iron parameters. METHODS: 20 dialysis patients received a total of 26 infusions of FeGl. A rapid infusion of 135 mg (Protocol A (n=10)) or 62.5 mg (Protocol B (n=7)) of FeGl was given during the last 30 min of dialysis. A slow infusion of 125 mg (Protocol C (n=9)) or 62.5 mg (Protocol D (n=10)) was given during 4 or 4.5 h of dialysis. Blood was taken at regular intervals, before, during, and after dialysis for determination of serum iron, transferrin, ferritin, haematocrit, total protein, albumin, and lactate dehydrogenase (LDH). Transferrin saturation was calculated from transferrin and serum iron. RESULTS: With rapid infusion A (125 mg) the highest levels of serum iron (median 120 (range 40-159) micromol/l) and transferrin saturation (207 (84-331)%) were seen at the end of the infusion. These were significantly higher than the peak levels with B, C, and D (P相似文献   

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.     

In vitro chemosensitivity of chronic lymphocytic leukaemia to purine analogues--correlation with clinical course

OBJECTIVE: To compare the risk for diabetic retinopathy in non-Hispanic white, non-Hispanic black, and Mexican-American adults with type 2 diabetes in the U.S. population. RESEARCH DESIGN AND METHODS: Representative population-based samples of people aged > or = 40 years in each of the three racial/ethnic groups were studied in the 1988-1994. Third National Health and Nutrition Examination Survey (NHANES III). Diagnosed diabetes was ascertained by medical history interview, and undiagnosed diabetes by measurement of fasting plasma glucose. A fundus photograph of a single eye was taken with a nonmydriatic camera, and a standardized protocol was used to grade diabetic retinopathy. Information on risk factors for retinopathy was obtained by interview and standard laboratory procedures. RESULTS: Prevalence of any lesions of diabetic retinopathy in people with diagnosed diabetes was 46% higher in non-Hispanic blacks and 84% higher in Mexican Americans, compared with non-Hispanic whites. Blacks and Mexican Americans also had higher rates of moderate and severe retinopathy and higher levels of many putative risk factors for retinopathy. Blacks had lower retinopathy prevalence among those with undiagnosed diabetes. In logistic regression, retinopathy in people with diagnosed diabetes was associated only with measures of diabetes severity (duration of diabetes, HbA1c, level, treatment with insulin and oral agents) and systolic blood pressure. After adjustment for these factors, the risk of retinopathy in Mexican Americans was twice that of non-Hispanic whites, but non-Hispanic blacks were not at higher risk for retinopathy. These risks were similar when people with undiagnosed diabetes were included in the logistic regression models. CONCLUSIONS: The prevalence and severity of diabetic retinopathy is greater in non-Hispanic blacks and Mexican Americans with type 2 diabetes in the U.S. population than in non-Hispanic whites. For blacks, this can be attributed to their higher levels of risk factors for retinopathy, but the excess risk in Mexican Americans is unexplained.     

Serum transferrin receptor concentration is not indicative of erythropoietic activity in chronic hemodialysis patients with poor response to recombinant human erythropoietin

BACKGROUND: Serum transferrin receptor (sTfR) is a transmembrane glycoprotein derived from erythroid precursors in the bone marrow. Its concentration provides a quantitative measure of total erythropoietic activity and an indication of functional iron deficiency. This study was conducted to investigate whether sTfR is a useful index of erythropoietic activity in chronic hemodialysis patients with poor response to maintenance recombinant human erythropoietin (rHuEPO) therapy. METHODS: Using an enzyme-linked immunosorbent assay, sTfR concentration was measured in 67 uremic patients who had been on hemodialysis for a mean of 42 months (3-242 months). rHuEPO was administered three times a week to keep the hematocrit above 30%. Hemoglobin, red blood cell indices, serum ferritin, serum total iron binding capacity and unsaturated iron binding capacity were determined. Of the 67 patients, 35 who responded favorably to rHuEPO with hematocrits above 30% were categorized as Group I and 32 who did not attain the target hematocrit were categorized as Group II. As a control group, 31 healthy subjects were also investigated. RESULTS: The serum iron, ferritin, transferrin iron saturation, dialysis efficiency and nutritional state were not different between groups of hemodialysis patients. The mean sTfR concentration was 2.1 +/- 0.6 micrograms/ml (range, 1.15-3.53 micrograms/ml) in Group I patients, compared with 1.9 +/- 0.9 micrograms/ml (range, 1.03-2.65 micrograms/ml) in Group II. The difference was not significant. In addition, the mean sTfR concentration of 1.8 +/- 0.4 micrograms/ml (range, 0.86-2.76 micrograms/ml) in the healthy controls was not significantly different from Groups I and II. CONCLUSIONS: sTfR concentration cannot be used to distinguish good from poor rHuEPO responders among chronic hemodialysis patients who have elevated serum ferritin (> 300 micrograms/l) and transferrin iron saturation (> 25%) during the course of maintenance rHuEPO therapy.     

Altered systemic iron metabolism in Parkinson's disease

Iron deposition in the substantia nigra in Parkinson's disease has been associated with an increase in lactoferrin receptors and a reduction in ferritin concentration. This accumulation of iron in the brain may accelerate free radical formation, lipid peroxidation, and neuronal death. Remarkably, there are few data available concerning systemic iron metabolism in Parkinson's disease. We measured total iron binding capacity and circulating iron, ferritin, transferrin, and transferrin receptors; calculated transferrin saturation; and estimated dietary iron intake in patients with idiopathic Parkinson's disease and in controls. Concentrations of circulating iron, ferritin, and transferrin as well as total iron binding capacity and transferrin saturation were significantly lower in patients than controls. There were no differences in transferrin receptors or dietary intake of iron. The decrease in levels of systemic ferritin and transferrin and the total iron binding capacity parallels observations in a Parkinson's disease brain, but the reductions in serum iron concentrations and transferrin saturation do not, and were unexpected. These results suggest the existence of a defect in the systems that regulate the synthesis of the major proteins of iron metabolism in the liver as well as the brain in Parkinson's disease that may, over time, expedite entry of iron into the brain and decrease iron in the extracellular compartment.     

Thrombolytic eligibility

OBJECTIVE: To evaluate the prevalence and time trends for diagnosed and undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults by age, sex, and race or ethnic group, based on data from the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) and prior Health and Nutrition Examination Surveys (HANESs). RESEARCH DESIGN AND METHODS: NHANES III contained a probability sample of 18,825 U.S. adults > or = 20 years of age who were interviewed to ascertain a medical history of diagnosed diabetes, a subsample of 6,587 adults for whom fasting plasma glucose values were obtained, and a subsample of 2,844 adults between 40 and 74 years of age who received an oral glucose tolerance test. The Second National Health and Nutrition Examination Survey, 1976-1980, and Hispanic HANES used similar procedures to ascertain diabetes. Prevalence was calculated using the 1997 American Diabetes Association fasting plasma glucose criteria and the 1980-1985 World Health Organization (WHO) oral glucose tolerance test criteria. RESULTS: Prevalence of diagnosed diabetes in 1988-1994 was estimated to be 5.1% for U.S. adults > or = 20 years of age (10.2 million people when extrapolated to the 1997 U.S. population). Using American Diabetes Association criteria, the prevalence of undiagnosed diabetes (fasting plasma glucose > or = 126 mg/dl) was 2.7% (5.4 million), and the prevalence of impaired fasting glucose (110 to < 126 mg/dl) was 6.9% (13.4 million). There were similar rates of diabetes for men and women, but the rates for non-Hispanic blacks and Mexican-Americans were 1.6 and 1.9 times the rate for non-Hispanic whites. Based on American Diabetes Association criteria, prevalence of diabetes (diagnosed plus undiagnosed) in the total population of people who were 40-74 years of age increased from 8.9% in the period 1976-1980 to 12.3% by 1988-1994. A similar increase was found when WHO criteria were applied (11.4 and 14.3%). CONCLUSIONS: The high rates of abnormal fasting and postchallenge glucose found in NHANES III, together with the increasing frequency of obesity and sedentary lifestyles in the population, make it likely that diabetes will continue to be a major health problem in the U.S.     

Drug use patterns and gender differences among heroin addicts hospitalized for detoxification

OBJECTIVE: To evaluate the role of genetic testing in screening for hereditary hemochromatosis to help guide clinicians, policymakers, and researchers. PARTICIPANTS: An expert panel was convened on March 3, 1997, by the Centers for Disease Control and Prevention (CDC) and the National Human Genome Research Institute (NHGRI), with expertise in epidemiology, genetics, hepatology, iron overload disorders, molecular biology, public health, and the ethical, legal, and social implications surrounding the discovery and use of genetic information. EVIDENCE: The group reviewed evidence regarding the clinical presentation, natural history, and genetics of hemochromatosis, including current data on the candidate gene for hemochromatosis (HFE) and on the ethical and health policy implications of genetic testing for this disorder. CONSENSUS PROCESS: Consensus was achieved by group discussion confirmed by a voice vote. A draft of the consensus statement was prepared by a writing committee and subsequently reviewed and revised by all members of the expert group over a 1-year period. CONCLUSIONS: Genetic testing is not recommended at this time in population-based screening for hereditary hemochromatosis, due to uncertainties about prevalence and penetrance of HFE mutations and the optimal care of asymptomatic people carrying HFE mutations. In addition, use of a genetic screening test raises concerns regarding possible stigmatization and discrimination. Tests for HFE mutations may play a role in confirming the diagnosis of hereditary hemochromatosis in persons with elevated serum iron measures, but even this use is limited by uncertainty about genotype-phenotype correlations. To address these questions, the expert group accorded high priority to population-based research to define the prevalence of HFE mutations, age and sex-related penetrance of different HFE genotypes, interactions between HFE genotypes and environmental modifiers, and psychosocial outcomes of genetic screening for hemochromatosis.     

Cost-effectiveness analysis of serum ferritin screening in periodic physical examinations of women at the fertile age

BACKGROUND: Fertile-aged women are a population group at special risk for developing ferropenia. In the periodic health care examinations, hemogram, among other tests, are included to detect the most advanced state of iron deficity, ferropenic anemia. Likewise, preanemic ferropenia presents a certain morbidity. The aim of this study was to analyze the cost-effectiveness of screening serum ferritin determination in health care examinations of fertile-aged women. SUBJECTS AND METHODS: An observational transversal study was carried out in 322 women in whom hemogram and serum ferritin were determined. The effects of serum ferritin determination were simulated in a hypothetical cohort of 20-year old women annually examined up to the age of 50 years (mean age of menopause). RESULTS: The prevalence of preanemic ferropenia (serum ferritin < or = ng/ml) was 44.1% and that of ferropenic anemica (Hb < 120 g/l and serum ferritin < or = 25 ng/ml) was 3.4%. Hemogram sensitivity for detection of ferropenia was 7.2% (3.6-12.5). By means of the screening program with serum ferritin avoiding of one year with ferropenia costs 2,428 pesetas. Prolonging the program to longer than 35 years largely increases the marginal cost. Cost-effectiveness analysis is specially sensitive to the cost of the diagnostic tests and disease prevalence. CONCLUSIONS: Ferropenia in fertile-aged women is a frequent disorder. Avoiding ferropenia by early diagnosis may be performed at a relatively low cost.     

The role of serum transferrin receptor in the diagnosis of iron deficiency

BACKGROUND AND OBJECTIVE: Iron deficiency anemia (IDA) is often associated with inflammatory disorders. The most conventional parameters of iron metabolism are therefore affected, making the evaluation of iron status difficult. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes. The aim of this study was to investigate the role of sTfR in differentiating IDA with inflammatory features. DESIGN AND METHODS: A diagnostic study of sTfR measured by immunoassay was carried out in IDA and anemia of chronic disorders (ACD). The cut-off points of sTfR and the ratio of sTfR/serum ferritin, which were obtained after comparing IDA and ACD, were applied to a group of 64 patients with mixed iron patterns (MIX) (16 with ACD and 48 with IDA). RESULTS: The best cut-off point of sTfR between IDA and ACD was 4.7 mg/L. Applying this cut-off to the MIX group, an efficiency of 87% was obtained (sensitivity 92% and specificity 81%). This level of sTfR correctly classified 53 out of 64 cases of the MIX group (83%). Using the ratio of sTfRx 100/serum ferritin, the best cut-off point was 8 (efficiency 100%), which correctly classified 62 out of 64 cases of the MIX group (97%). INTERPRETATION AND CONCLUSIONS: This study demonstrates that sTfR in conjunction with other iron parameters is very useful in iron deficiency evaluation, especially in hospital practice. Iron treatment should be considered in patients with mixed patterns of iron status, in which the diagnosis of IDA versus ACD is difficult, when the levels of sTfR exceed the cut-off point.     

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.