Introduction Hereditary haemochromatosis (HH) is the most common genetic abnormality in populations of Northern European ancestry. There are limited data on the frequency of HFE in populations from the Indian subcontinent. Elevated serum ferritin (Fe) and transferrin saturation (TSAT) are often used as the basis for referral for HFE gene analysis.

Aim We undertook this study to evaluate the performance of elevated Fe and TSAT in the diagnostic algorithm of HH in a Caucasian population and how it compared when applied to an Indian population.

Method Data on all patients referred from the gastroenterology service for HFE gene analysis between 2001 and 2009 were evaluated. Serum Fe and TSAT were recorded where available to assess their utility in predicting HFE gene mutations and subsequent requirement for venesection. An estimation of the prevalence of iron overload due to HFE gene mutations in our large Indian population was sought.

Results 307 patients with elevated Fe levels underwent HFE genetic analysis. 146/307 (48%) patients had a TSAT performed at the time of referral. 34/307 (11%) were homozygotes for C282Y mutation, while 18 (6%) were compound heterozygotes. Almost half of those tested 147/307 (48%) had no genetic mutation.

A TSAT >45% was found in 42/146 tested patients. All C282Y/C282Y patients tested had a TSAT >45%, almost a quarter of whom (23.5%) had a TSAT <55%. All WT/WT patients with a TSAT >45% had alcoholic liver disease. The positive predictive value of a TSAT >45% in detecting a C282Y/C282Y or C282Y/H63D mutation was 54.7% compared to 14.5% for ferritin. The negative predictive value of a TSAT >45% in excluding a C282Y/C282Y or C282Y/H63D mutation was 96.2%. 32/307 (10.4%) patients from the Indian sub-continent underwent HFE genetic testing. The mean Fe was 421 with a mean TSAT of 40.3% compared to 564 and 47.7%, respectively, for the Caucasian population (p<0.05.) In this subgroup, there was one H63D/H63D mutation and 6 (19%) H63D/WT heterozygotes. None had a C282Y mutation. TSAT had a NPV of 100% in excluding clinically significant HH.

Conclusion TSAT has an excellent NPV and should be an integral part of the diagnostic algorithm for HH, where a cut-off value of 45% detects all C282Y homozygotes, while a higher cut-off value may miss some patients. This translates well into Indian populations. HFE gene mutations are extremely rare in patients of Indian descent and other aetiologies for elevated Fe/TSAT should be sought.