Population Screening for Haemochromatosis: A Unifying Analysis of Published Intervention Trials

Abstract

Objectives-To examine the efficacy of population screening for haemochromatosis by analysing the screening performance of seven intervention trials, and to compare this with the expected performance derived from family studies. Setting-Seven population intervention trials carried out between 1983 and 1995 in Australia, Scandinavia, Iceland, and the United States. Methods-Seven of 23 English language trials identified were suitable for the meta-analysis. Transferrin saturation and serum ferritin measurements derived from family studies were used to predict detection and false positive rates for each trial. Results-The seven trials used various screening and diagnostic criteria. A total of 18 396 men and 12 254 women were screened. Because some cases were not detected by screening, and some screen positive individuals did not complete diagnostic testing, the prevalence of homozygous individuals was underestimated in all the trials. The reported and predicted percentages of screen positive individuals nearly always agreed. The homozygote prevalence was estimated to be 34 men and 40 women per 10000 (prevalence predicted from family studies is 53 per 10 000). Clinical manifestations were present in 50% of male and 44% of female homozygotes. Conclusions-False positive rates, homozygote prevalences, and frequency of clinical manifestations were in general agreement with predictions from family studies. However, incomplete understanding about a number ofissues requires that further pilot trials be carried out before screening can be considered part of routine medical practice.

Prevalence of iron deficiency and anemia among healthy women of reproductive age in Bhaktapur, Nepal

“…Approximately 3.3 million women of childbearing age and 240,000 children aged 1-2 years have iron-deficiency anemia (45 ); conversely, up to one million persons in the United States may be affected by iron overload due to hemochromatosis (106,107 ) . Hemochromatosis is a genetic condition characterized by excessive iron absorption, excess tissue iron stores, and potential tissue injury.…”

Public health aspects of genetic screening for hereditary haemochromatosis in Australia

“…In a pooled analysis of case-control studies the estimated penetrance for iron overload in C282Y homozygotes was between 31 and 94%, depending on the prevalence of iron overload due to disease and the prevalence of C282Y homozygosity. 11 An earlier pooled analysis of seven population-based studies 16 estimated penetrance to be 50% for males and 44% for females. The Busselton study in Wester n Australia found penetrance of C282Y homozygosity for raised serum fer ritin was 58% 14 based on 12 homozygotes.…”

Hereditary hemochromatosis: Perspectives of public health, medical genetics, and primary care

“…16,23 The wide range of estimates reported in these studies reflects differences in study characteristics noted previously; however, all observe a drop-off in subjects with positive test results with each step in the testing pathway (Table 1). 24 25 evaluated this question in a review of population-based studies. The studies were included if they confirmed iron overload by liver biopsy or quantitative phlebotomy and collected information on clinical complications, including liver fibrosis, liver cirrhosis, cardiomyopathy, arthropathy, diabetes, abdominal pain, and hepatomegaly.…”

“…Similarly, a population-based study using TS level as the primary screening method found fewer women than men with significant morbidity. 28 Bradley et al 25 calculated the weighted average for prevalence of iron overload to be 0.25%; correcting for missed diagnoses and compliance, the authors estimated actual prevalence of iron overload to be 0.5% in men and 0.6% in women. 25 Other studies suggest a prevalence of iron overload ranging from 0.06% to 0.4%.…”

“…28 Bradley et al 25 calculated the weighted average for prevalence of iron overload to be 0.25%; correcting for missed diagnoses and compliance, the authors estimated actual prevalence of iron overload to be 0.5% in men and 0.6% in women. 25 Other studies suggest a prevalence of iron overload ranging from 0.06% to 0.4%. 24 Assuming that one third to one half of people with iron overload have clinical symptoms, these figures suggest that the prevalence of clinical disease due to iron overload is in the range of 0.02% to 0.25%.…”