Maladie de Gaucher : diagnostic, suivi et traitement

Abstract

Gaucher disease type 1 (GD1) is a rare, multisystem disease caused by a genetic deficiency of lysosomal glucocerebrosidase. Glucocerebroside accumulates in cells of the reticuloendothelial system leading to chronic macrophage activation, bone marrow infiltration, organ enlargement (liver and spleen) and cytopenia. Skeletal manifestations are often the most striking and disabling long-term consequence of GD1; clinical or radiographic evidence of bone disease has been reported in 70–100% of diagnosed patients. Avascular osteonecrosis of the hip is the most disabling complication with early bone pain and often-joint collapse and secondary osteoarthritis needing orthopaedic interventions in young adults. Localized or systemic bone fragility explains osteopenia, osteoporosis and fractures. Although no double-blind randomized studies have been performed to evaluate bone effect of the treatments, enzyme replacement therapy has demonstrated its efficacy in naïve patients reducing bone pain in about 50% of patients within 1 to 2 years and improving bone mineral density after at least 3 years of treatment. Substrate reduction therapy (miglustat) improved in open-label bone pain and bone marrow infiltration. Specific treatment of bone fragility, for example with bisphosphonates, needs a rigorous evaluation with assessment for other risk factors.