High prevalence of the Cys282Tyr HFE mutation facilitates and improved diagnostic service for hereditary haemochromatosis in South Africa

Objective. The aim of the study was to investigate the molecular basis of h ereditary haemochromatosis (HH) in South Africa in order to establish a rel iable, cost-effective molecular diagnostic service for this potentially let hal disorder. Design. DNA samples of patient and control groups were screened for two com mon haemochromatosis (HFE) gene mutations. The local frequencies of mutatio ns C282Y and H63D were determined and the DNA results correlated with bioch emical parameters. Setting. Patients were referred from private practitioners, health workers and pathologists for a molecular diagnosis of HH at the University of Stell enbosch Medical School. Twenty-two of the 244 referrals were clinically dia gnosed with HH, while the remaining patients were family members of the pro bands or unrelated subjects referred solely on the basis of an abnormal iro n profile. Results. Seventeen of the 22 patient referrals (77%) diagnosed with HH were homozygous for the C282Y mutation, 3 (14%) were compound heterozygotes for mutations C282Y and H63D, and 2 patients (9%) did not exhibit either mutat ion. Screening of 458 control individuals from the general South African po pulation demonstrated a carrier frequency of approximately 17% for the C282 Y mutation among whites, implying that up to 1 out of every 115 South Afric ans of European descent may be homozygous for this founder-type mutation. A mong 64 healthy blood donors of mixed ancestry, we detected 2 individuals h eterozygous and 1 homozygous for the C282Y mutation. Conclusions. The detection of mutations C282Y and H63D at a high frequency in the majority of affected South African patients facilitates accurate pre -clinical and confirmatory diagnosis of HH in South Africa. Early detection by DNA screening and subsequent treatment by repeated phlebotomy can preve nt disease onset in affected individuals. DNA diagnosis is particularly app licable to a common genetic disease such as HH, which is underdiagnosed and potentially lethal, but treatable.