A prospective study to identify clinically symptomatic hereditary hemochromatosis patients

Hereditary hemochromatosis (HH) is an iron overload disease eventually causing organ failure. The majority of symptomatic patients harbor the C282Y homozygous mutation in the HFE gene. The classical clinical picture is hepatomegaly, skin hyperpigmentation and diabetes. Clinically symptomatic patients have high morbidity and increased mortality as compared to the general population. Due to the low penetrance of the frequent (0.5% prevalence in Austria) HFE gene mutation, general screening is however currently not recommended. Thus, targeted approaches in high- risk populations should be defined. We have previously delineated musculoskeletal symptoms in HH patients. In fact, articular involvement is the most frequent clinical manifestation in HH. Interestingly, joint pain is indeed the first clinical manifestation in many cases and precedes diagnosis by 5 years. Others and we found that these patients present with signs and symptoms indistinguishable from primary osteoarthritis (OA). However, affected anatomical sites differ substantially from primary OA: Metacarpophalageal and ankle joints are often affected in HH but rarely in primary OA. Moreover, hemochromatosis causes severe OA to hip but not knee joints. Importantly, hip joint replacement surgery occurs much earlier in life in HH patients. Thus, a targeted screening of patients undergoing hip joint replacement surgery could identify clinically symptomatic HH patients. In this study, we will prospectively include all patients below the age of 70 undergoing joint replacement surgery of the hip at three large orthopedic centers in Vienna and Salzburg over a period of two years. All patients will have an epidemiological, clinical- rheumatological examination and assessment of iron status. This study will provide evidence, whether a targeted screening approach can identify HH patients in a high- risk population.

Hereditary hemochromatosis is an iron overload disease causing significant organ damage. In the majority of patients, mutations in the HFE gene are the cause. Symptomatic patients have a high morbidity and elevated mortality as compared to the general population. A general screening approach is currently not recommended despite the estimated prevalence of 0.5% in Austria. This is related to the fact, that that not all individuals with HFE gene mutations develop overt hemochromatosis.Joint pain is the most frequent symptom in hemochromatosis. Finger joints, wrists, hip and ankle joints are typically affected in these patients. Musculoskeletal problems often precede diagnosis by several years. We have previously found, that hemochromatosis is associated with an elevated risk for hip joint replacement before the age of 70. Therefore, we conducted a screening study on the presence of hereditary hemochromatosis in patients undergoing hip joint replacement surgery before the age of 70. In almost one thousand patients screened, we could not identify more hemochromatosis patients as compared to a control group from the general population. Thus, screening of younger patients with end-stage hip osteoarthritis for iron overload cannot be recommended on the basis of our study.