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.