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Analysis of the common C282Y and H63D mutations in the HFE gene is widely used to diagnose hereditary hemochromatosis (HH). The aim of this study was to evaluate the efficiency with which different hospitals and general practitioners select patients for HH genotype and to determine the distribution of HFE mutations in such patients. Nine hundred unrelated patients from Danish hospitals and general practitioners (group A) and 69 consecutive patients from a specialized liver unit (group B) were examined for HFE substitutions using multiplex real-time polymerase chain reaction. In group A we found 13.0% (0%) C282Y homozygotes, 5.8% (2.6%) H63D/C282Y compound heterozygotes and 1.9% (3.1%) S65C heterozygotes. The values for 420 Danish blood donors are shown in parentheses. The distribution of genotypes in group B was similar to that of the blood donors. Serum ferritin, transferrin iron saturation and pathological data were collected from 38 randomly selected C282Y homozygotes, 36 H63D/C282Y compound heterozygotes, 19 H63D heterozygotes, 17 S65C heterozygotes and 144 wild-types. All of the C282Y homozygotes and 28% of the compound heterozygotes were diagnosed as HH patients. There was no evidence of HH in the H63D homozygotes or S65C heterozygotes. Moreover, 7 wild-type patients, 2 C282Y heterozygote patients and one H63D heterozygote patient fulfilled the criteria for HH. The significant enrichment of HH among associated genotype samples submitted for HFE testing indicates that the clinical selection is generally adequate. However, the study showed substantial deviation in the selection efficiency among the various hospitals and general practitioners. [ABSTRACT FROM AUTHOR]

The object was to analyze, in a nationwide survey, the incidence and course of hereditary hemochromatosis in relation to the degree of iron overload and the presence of organ damage. The study included 179 Danish Caucasian patients with clinically overt hemochromatosis diagnosed between 1948 and 1985. A cohort of 158 patients was followed for a median of 8.5 years (range: 0.2–29.5). From 1951 to 1975, the yearly relative incidence rate was constant: 0.58/100,000 persons >20 years of age. From 1981 to 1985, the yearly relative incidence rate rose to 1.40/100,000 persons >20 years of age. Survival was reduced in the entire series when compared with a matched control population (p<0.0001). There was a steady increase in survival from 1948 to 1985 (p<0.002). Survival was significantly reduced in patients with liver cirrhosis and/or diabetes mellitus (p<0.01). In contrast, survival in patients without cirrhosis or diabetes was similar to rates expected. Survival in patients with arthropathy was higher than in patients without joint affection (p<0.004). Patients adequately treated with phlebotomy (n=66) had a higher survival than inadequately treated patients (n=62; p<0.0001). Adequately treated patients with cirrhosis and/or diabetes had better survival than inadequately treated patients with similar organ damage (p<0.001). The main causes of death were hepatic failure due to cirrhosis (32.0%) and cirrhosis with liver cancer (23.1%). Sharpened diagnostic awareness has improved early diagnosis and increased the diagnostic frequency of clinical hemochromatosis. Adequate phlebotomy treatment was the major determinant of survival and markedly improved prognosis. Early detection and treatment of this common iron overload disorder is crucial and can completely prevent any excess mortality caused by hemochromatosis. [ABSTRACT FROM AUTHOR]

Iron status, i.e. serum ferritin and haemoglobin (Hb) levels, was assessed in a population survey in 1994 (Dan-Monica 10) comprising 1319 Caucasian Danish women in age cohorts of 40, 50, 60 and 70 years. In the entire series, ferritin levels increased significantly from 40 years to 60 years of age. The prevalence of small iron stores (ferritin 16–32 μg/l), depleted iron stores (ferritin <16 μg/l) and of iron deficiency anaemia (ferritin <13 μg/l and Hb <121 g/l) decreased steadily with age. Blood donors (n=109) had lower ferritin levels than non-donors (P<0.0001). Ferritin levels in donors were inversely correlated with the cumulated number of lifetime phlebotomies (rs=–0.25, P<0.01). Ferritin levels in non-donors (n=1208) were low in 40-year-old women (median 40 μg/l) and increased to a median of 95 μg/l in 60- and 70-year-old women (P<0.0001). In non-donors 40 years of age, the prevalence of small iron stores was 40.4%, the prevalence of depleted iron stores 10.8% and the prevalence of iron deficiency anaemia 2.16%. The prevalence of iron overload (ferritin >300 μg/l) was 1.54%. Ferritin levels in 60- and 70-year-old non-donors were correlated with the body mass index (rs=0.11, P=0.01). Ferritin levels in 50- to 60-year-old non-donors were correlated with alcohol intake (rs=0.23, P<0.0001). In the entire series, 37.5% of non-donors took supplemental ferrous iron (median 14 mg iron per day). Iron supplements had a significant positive influence on iron status in 40-year-old premenopausal non-donors but no effect in postmenopausal women or in donors. Non-donors (n=170) treated with acetylsalicylic acid had lower ferritin levels (median 55 μg/l) than non-treated (n=1038; median 75 μg/l) (P<0.0001). Compared with the Dan-Monica 1 iron status survey in 1984, the prevalence of iron deficiency and iron deficiency anaemia was unchanged, whereas the prevalence of iron overload displayed a slight increase. The 1987 abolition of the mandatory iron fortification of flour apparently had no negative effect on iron status. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to examine the relationships between serum ferritin and risk factors for ischaemic heart disease (physical activity, body mass index, tobacco smoking, alcohol consumption, serum total cholesterol, serum triglycerides, serum high-density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressures).Design: Epidemiological population survey performed at the Copenhagen County Centre for Prevention of Disease in 1982-84.Subjects: The participants were selected at random from the census register and comprised 2235 healthy Caucasian Danes, all non-blood-donors (1044 men and 1191 women), in cohorts of 30, 40, 50 and 60 years of age. The participants gave a detailed medical history and had a clinical examination including blood samples.Main Outcome Measures: In both men and women, all risk factors displayed a significant increase with age. In men aged 40-60 years, significant positive associations were found between serum ferritin and the following risk factors: body mass index, alcohol intake, serum triglycerides, and systolic and diastolic blood pressures. There was a significant negative association between serum ferritin and tobacco smoking. There was no association between serum ferritin and physical activity, serum total cholesterol or serum HDL cholesterol. In women aged 40-60 years, significant positive associations were found between serum ferritin and the following risk factors: body mass index, alcohol intake and serum triglycerides. There was no association between serum ferritin and physical activity, tobacco smoking, serum total cholesterol, serum HDL cholesterol or blood pressure.Conclusions: Associations were found between serum ferritin and some risk factors for ischaemic heart disease in men and women. The clinical significance of these findings remains to be clarified. One may hypothesize that the 'missing link' between serum ferritin and ischaemic heart disease in men is the relationship between serum ferritin, serum triglycerides and blood pressure. [ABSTRACT FROM AUTHOR]