Severe skeletal complications in Japanese patients with type 1 Gaucher disease

To better characterize skeletal complications in Japanese patients with type 1 Gaucher disease (GD), we performed genotyping and clinical and radiological analysis of 35 patients, the vast majority of this population, Skeletal complications tend to be very common, severe and rapidly progressive in Japanese patients with type 1 GD. Twenty (57%) of these patients manifested end points of severe bone disease including avascular necrosis, pathological fracture and/or bone crisis. Mean time from presentation/diagnosis of GD until presentation of this involvement was 3 years 6 months±4 years 1 month. Prevalence of severe bone disease is significantly higher in splenectomized than in non-splenectomized patients – 81% (17/21) versus 21% (3/14) (p=0.0007, Fisher's exact test). Four (29%) of 14 patients receiving enzyme replacement therapy (ERT) or bone marrow transplantation (BMT) manifested severe bone involvement for the first time during or after treatment. All cases occurred in children in whom ERT doses had been lowered after only brief administration of higher starting doses (n=3) or partial donor marrow engraftment resulted in low glucocerebrosidase (GCR) activity (n=1). These observations suggest that splenectomy may correlate with accelerated skeletal deterioration with severe skeletal disease, at least in patients with severe phenotypic expression. They also suggest that it is important that sufficient GCR is available in paediatric patients with severe phenotypic expression. Hence ERT dosages should be based on disease severity and on age, with sustained administration of full doses in patients at greater risk of important skeletal complications.