Warnich L, Koegelenberg AJ

University of Stellenbosch, Stellenbosch, South Africa

The incidence of variegate porphyria (VP) in the South African population of European descent is the highest in the world because of a founder gene effect and the gene frequency was estimated to be 0.3%. However, this estimate is questionable on the grounds of genealogical and biochemical methods used and as indicated by more recent records from diagnostic laboratories. According to earlier reports more than 80% of the estimated 10 000-20 000 South African individuals with VP remain undetected and are therefore at risk of potentially lethal acute neurological attacks. This poses a serious question regarding the actual frequency of VP, and specifically the founder gene mutation, in South Africa. Are there thousands of undiagnosed VP carriers in South Africa as genealogical studies and population growth curves have predicted, or is the allele frequency much lower than 0.3%? The aim of this study was thus to determine the prevalence of the founder mutation (R59W) with a highly specific DNA test. Blood samples were obtained at blood transfusion clinics, pathology clinics and maternity wards. For the initial screening we used SSCP analysis, which proved to be consistent and cost-effective. All R59W positive samples were re-tested using restriction enzyme analysis. The R59W mutation was detected in five of the 4637 samples collected to date. The estimated frequency of 0.15% (5/3311) for the founder mutation in South Africans of European descent is much lower than the frequency of 0.3% estimated previously. However, different frequencies were obtained within the various population samples and we suggest that a newborn baby population sample be used in the future, as it is the most unbiased sample source. Interestingly, the highest frequency for the R59W mutation was obtained in this sample. One of the two adult R59W positive participants was unaware of her carrier status, in accordance with the incomplete penetrance of the trait. Two of the mothers of the three newborn babies found to be R59W positive were also not aware of VP in their families, indicating that ignorance regarding VP status in South Africa is a matter of some concern.