Poster (15W146)

Clinical audit of the genotypic frequencies of Hereditary Haemochromatosis referrals to Cork University Hospital 2009-2012


McDonald, C., Joyce, C, Su, Y*., Crosbie, O


Department of Hepatology and Clinical Biochemistry, Cork University Hospital Department of Statistics, University of Hawaii at Manoa, USA*


Hereditary Haemochromatosis (HH) defines a complex heterogeneous group of autosomal recessive disorders that result in multi organ iron overload with the liver parenchymal cells being primarily affected. Our study concentrated on HFE- related haemochromatosis, the most common cause of HH.


Clinical expression of HH is variable with the C282Y homozygous genotype representing the largest group. However, even within this group, approximately 75-85% do not develop HH owing predominantly to its varied penetrance. There have been few studies extensively reviewing genotype population frequencies in Ireland to date. Our study aims to assess the frequencies of the various genotypes recorded from referrals to CUH. A further objective is to correlate the different genotypes with biochemical iron overloading to establish any statistically significant variations in altering the percentage Transferrin saturation (TS%) cutoff for Iron Overload.


The audit encompasses a retrospective review of referrals for HH genotype testing to the Clinical Biochemistry Department from the periods August 2009 to December 2012. The referrals were divided into Diagnostic, Predictive and Carrier Status groups as per best practice guidelines. Iron overload was defined into two groups; TS >45% and TS >55%. Data was anonymised and the following variables were recorded on each patient: Ethnicity, Age, Sex, Referrer, TS, Ferritin, Comorbidities (Elevated LFTs, Cardiomyopathy, DM, Arthritis) and HH genotype. Genotyping was performed using fluorescent PCR for HFE mutations p.Cys282Tyr (C282Y), p.His63Asp (H63D) and p.Ser65Cys (S65C). All analyses for the project were conducted using Statistical Analysis System.


A total of 2,511 referrals were included in the study. The predominant age was 35- 65 years (65% of total). Diagnostic referrals accounted for 62% (1,517) of total with GP’s making 93% of referrals. The overall genotype frequencies showed C282Y homozygous represented 20% of the overall population (497 patients), compound heterozygotes recorded at 13% (329 patients) and C282Y carriers were seen in just over a quarter of the population (26%). Above 55%, C282Y homozygous patients represent 75% of HH diagnoses. In a cohort of 139 patients with “severe” biochemical overload with TS>45% and Ferritin >1,000, an expected majority were C282Y homozygous (53%). “Normal” patients without a HFE mutation accounted for 20% of these severe iron overloaded patients.


This study shows a high carrier rate of C282Y among the population (26%). C282Y specificity rises dramatically above levels of TS>55%. There remains an unexplained high level of the population (20%) with normal genotyping and severe biochemical iron overload. This finding requires further investigation.