Osteoarthritis [119–126]

Background: C282Y homozygous (HZ) variants of HFE gene are associated with iron overload disorders and premature osteoarthritis (OA). The link between C282Y-hetrozygosity (HT) and musculoskeletal problems is less clear. The H63D mutation is usually not associated with iron overload even if HZ. No definite association has been proven between HT- H63D alleles and their phenotype; however, compound HT with both the above variants has been known to cause haemochromatosis. This paper describes the prevalence and associations of the various HFE gene mutations in patients presenting to our midlands rheumatology unit with features of OA. Methods: 100 consecutive patients most recently screened for the HFE gene were identified from our Dept records. Our indication for screening is premature, aggressive, inflammatory or focal small joint OA ie ‘exceptional OA’. The presence, type and allele variations of the HFE mutations were noted along with demographic data. The clinical, laboratory and radiographic features, the associated diagnosis and therapeutic interventions were recorded. Results: 41 patients (26 F) had confirmed HFE gene mutations amongst the 100 patients screened; mean age at point of screening was 53 yrs (range 27–82) and the mean duration of joint symptoms was 5.5 yrs. All the 41 patients were Caucasian. 6 cases (15%) were HZ of which 3 had C282Y mutation and had haemochromatosis requiring venesection. The other 3 were HZ for H63D of which 2 had mild ferritinaemia. 35 cases (85%) were HT for HFE of which 19 patients (54%) had the H63D variant, 11 patients (31%) had the C282Y variant and 4 had the S65Y type mutation. Ferritinaemia was uncommon in the H63D and C282Y HT groups (2, 6 respectively) but noted in 3 of the S65Y group. One case showing compound HT carrying both H63D and C282Y mutations was premenopausal with nodular small joint OA but normal ferritin. 28 patients in this group had arthralgia. The majority (23, 66%) had hand involvement followed by knees and feet in 14 and 11 patients respectively. Radiographic OA was confirmed in 17 patients with hand OA and 15 patients with large joint OA. 84% of the patients with H63D - HT had OA as did all patients with C282Y -HT genotype. NSAIDS were the mainstay in 18 patients with steroid injections beneficial in 15 patients; 6 went on to have surgery. Conclusions: 56% of the HFE gene mutations had the H63D variant making it the most frequent genotype compared with the 36% of the patients with C282Y varian