We maintain our own reference libraries on iron overload and haemochromatosis. References were also searched on PubMed. We used the search terms “hemochromatosis” and “haemochromatosis”. We mainly selected publications in the past 5 years, but did not exclude commonly referenced and highly regarded older publications. We also searched the reference lists of articles identified by this strategy and selected those we judged relevant. Our reference list was modified on the basis of comments
SeminarHaemochromatosis
Section snippets
Epidemiology
The diagnosis of haemochromatosis was based on phenotypic and historical measurements, including biochemical tests such as the transferrin saturation and serum ferritin tests, physical examination, family history, and often a liver biopsy. Since the introduction of a widely available DNA-based blood test, screening large populations to measure the prevalence of common mutations and genotypes of the haemochromatosis gene (HFE; chromosome 6p21.3) associated with haemochromatosis in white people
Pathophysiology
Identification of the genetic basis for HFE-associated and less common heritable types of haemochromatosis has led to a greater understanding of the function of HFE and other proteins that facilitate and regulate iron transport, especially in duodenal enterocytes, macrophages, and hepatocytes. Hepcidin, a polypeptide hormone produced in the liver, controls extracellular iron concentrations by binding to and inducing the degradation of the cellular iron exporter ferroportin.7 Concentrations of
Diagnosis
The first step in the diagnosis of haemochromatosis is to suspect the disorder, especially in patients who have unexplained liver dysfunction, hypogonadism, arthralgias or arthritis, or cardiomyopathy, or in those with first-degree relatives with haemochromatosis. For many years, transferrin saturation was endorsed as an ideal test for the assessment of possible haemochromatosis, because most C282Y homozygotes with iron overload have high transferrin saturation (>45% in women and >50% in men).
Clinical expression
Since the introduction of genetic testing in 1996, the presence of high serum ferritin concentrations has been used to assess the clinical expression of the HFE C282Y genotype. Serum ferritin concentrations are high in about 80% of men and 50% of women with C282Y homozygosity, and typically reflect the severity of iron overload (figure 2).
Studies of the signs and symptoms of haemochromatosis in C282Y homozygotes, identified by screenings that have included a control population, showed that the
Management
Phlebotomy therapy is still the cornerstone of treatment for iron overload in haemochromatosis.57 Patients undergo 500-mL phlebotomy every week until the serum ferritin concentration is about 20–50 μg/L. Some reports recommend phlebotomy to even lower concentrations of serum ferritin, and others doubt the effectiveness of phlebotomy therapy.58 The reason for lowering ferritin concentrations is to make sure that all potentially injurious iron deposits are removed. Because the rate of iron
Prevention
Haemochromatosis fulfils many but not all WHO criteria for a disease that is ideal for population screening: it is common, causes morbidity and mortality that can be prevented, can be diagnosed by available blood tests, and is readily treatable. However, the positive predictive value for a single-screening transferrin saturation measurement to detect C282Y homozygotes was only 2%27 in a primary-care population of 101 168 participants. Higher positive predictive values for transferrin saturation
Search strategy and selection criteria
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