Objective: The aim of the study was to investigate the molecular basis of hereditary haemochromatosis (HH) in South Africa in order to establish a reliable, cost-effective molecular diagnostic service for this potentially lethal disorder.
Design: DNA samples of patient and control groups were screened for two common haemochromatosis (HFE) gene mutations. The local frequencies of mutations C282Y and H63D were determined and the DNA results correlated with biochemical parameters.
Setting: Patients were referred from private practitioners, health workers and pathologists for a molecular diagnosis of HH at the University of Stellenbosch Medical School. Twenty-two of the 244 referrals were clinically diagnosed with HH, while the remaining patients were family members of the probands or unrelated subjects referred solely on the basis of an abnormal iron 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 mutation. Screening of 458 control individuals from the general South African population demonstrated a carrier frequency of approximately 17% for the C282Y mutation among whites, implying that up to 1 out of every 115 South Africans of European descent may be homozygous for this founder-type mutation. Among 64 healthy blood donors of mixed ancestry, we detected 2 individuals heterozygous 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 prevent disease onset in affected individuals. DNA diagnosis is particularly applicable to a common genetic disease such as HH, which is underdiagnosed and potentially lethal, but treatable.