Avascular Necrosis in Untreated Patients with Type 1 Gaucher Disease.

To determine the incidence of avascular necrosis (AVN) in untreated patients with type 1 Gaucher disease (GD1).

All patients with GD1 enrolled in the ICGG Gaucher Registry as of July 2007 were included in this analysis. All GD1 patients who either never received treatment or eventually went on to receive treatment were identified. Follow-up began on each patient's date of earliest reported assessment in the Registry. Among patients who never received treatment, follow-up continued until the last recorded assessment date in the Registry. For patients who eventually went on to receive treatment, follow-up continued until the date of initiation of therapy. Incidence rates (and Poisson exact 95% confidence intervals) of AVN were determined for both groups of patients. AVN was typically ascertained from X-Ray or MRI results.

As of July 2007, the inclusion criteria were met by 3,497 patients. The incidence rate of AVN among untreated patients was 22.8 per 1,000 person years (95% CI 20.2 to 25.7). Patients with antecedent splenectomy (total or partial) had a higher incidence rate of AVN (46.6 per 1,000 person-years, 95% CI 38.4 to 56.1) compared to patients without a splenectomy (incidence rate 17.0 per 1,000 person-years, 95% CI 14.5 to 19.8). The primary sites where AVN was identified in both groups were the hip and femur.

This is the first epidemiologic analysis to estimate incidence rates of AVN among untreated patients with GD1. Splenectomy appears to be a risk factor for GD1-associated AVN. Based on the incidence results above and presupposing equal risk distribution, without therapeutic intervention, most patients should theoretically experience at least one episode of AVN at some point in their life. However, because the GD1 population is genotypically and phenotypically heterogeneous, further analyses will attempt to identify characteristics that distinguish untreated patients at high risk of developing AVN from those who are less likely to develop this serious complication.

Mistry:Genzyme Corporation: Honoraria, Research Funding. Deegan:Genzyme Corporation: Honoraria. Vellodi:Genzyme Corporation: Honoraria, Speakers Bureau. Cole:Genzyme Corporation: Employment. Yeh:Genzyme Corporation: Employment. Weinreb:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees.