Iron Overload In Africa

Description

African iron overload is a distinct iron-loading disorder prevalent in Africa. Formerly termed Bantu siderosis, the disorder results from a predisposition to iron loading that is exacerbated by excessive intake of dietary iron. It is particularly a problem among Africans who drink a traditional beer brewed in non-galvanized steel drums. Although the disorder was once attributed to dietary excess alone, serious iron overload does not develop in all beer drinkers, and not all patients with iron overload consume excessive amounts of the beer (summary by Andrews, 1999).

Clinical Features

The pattern of iron deposition among persons with African iron overload differs from that among those with hereditary hemochromatosis (see 235200) (Gangaidzo et al., 1999). In the former persons, there is marked iron loading of Kupffer cells as well as hepatocytes, resembling the pattern seen in patients with transfusional siderosis and suggesting a defect in erythroid iron recycling. Cirrhosis, occasionally complicated by hepatocellular carcinoma, is the predominant organ manifestation. Cardiomyopathy and diabetes, common features of hereditary hemochromatosis, are less frequent. Although serum ferritin levels are elevated, the transferrin saturation does not always reflect the true extent of iron overload in these patients (summary by Andrews, 1999).

Patients with African iron overload are probably more susceptible than others to infection, and they appear to have an increased incidence of tuberculosis (Gordeuk et al., 1996; Moyo et al., 1997).

Inheritance

To examine the hypothesis that African iron overload also involves a genetic factor, Gordeuk et al. (1992) used likelihood analysis to test for an interaction between a hypothesized iron-loading locus and an environmental factor, namely increased dietary iron, to determine transferrin (190000) saturation and unsaturated iron-binding capacity. They studied 236 members of 36 African families chosen because they contained index subjects with iron overload. Among family members with increased dietary iron due to the consumption of traditional beer, transferrin saturation in serum was distributed bimodally, with 56 normal values and 44 elevated values; the mean serum ferritin concentration was 5 times higher in the subjects with elevated transferrin saturation. The pedigree analysis provided evidence of both a genetic effect (p less than 0.005) and an effect of increased dietary iron (p less than 0.005) on transferrin saturation and unsaturated iron-binding capacity. Gordeuk et al. (1992) found that, in the most likely model, increased dietary iron raised the mean transferrin saturation from 30 to 81% and lowered the mean unsaturated iron-binding capacity from 38 to 13 micro-mol per liter in subjects heterozygous for the iron-loading locus.

Moyo et al. (1998) presented evidence that heterozygosity for an unidentified iron-loading gene confers susceptibility to African iron overload and suggested that homozygous persons may be more severely affected.

Mapping

Gordeuk et al. (1992) excluded linkage of African iron overload to the HLA region (see 142800) on chromosome 6p21.3.

Molecular Genetics

In a study of 1,042 African chromosomes, Merryweather-Clarke et al. (1997) found a prevalence of 0% for the HFE C282Y mutation (613609.0001), the most common cause of hereditary hemochromatosis in persons of European descent. PCR analysis of DNA from 25 southern Africans, identified by segregation analysis as having a high probability of carrying the putative African iron-loading gene, failed to identify any subjects with the C282Y mutation (McNamara et al., 1998). Clinically significant iron overload occurs in Americans of African descent (Barton et al., 1995; Wurapa et al., 1996; Baer, 1996), but such persons rarely have mutations in the HFE gene (Monaghan et al., 1998).