Gaucher disease: risk stratification and comorbidities

Abstract

ABSTRACTIntroduction: Gaucher disease (GD) is characterized clinically by anemia, thrombocytopenia, hepatosplenomegaly and bone disease, with central nervous system (CNS) involvement for certain subtypes. In patients with GD type 1, which conventionally excluded those with primary CNS disease, bone complications represent a major source of morbidity. Some patients also have an increased risk of Parkinson disease (PD) and multiple myeloma (MM). There are several biomarkers, e.g., chitotriosidase and glucosylsphingosine, whose activity or concentrations have been correlated with overall disease burden.Areas covered: This paper reviews the authors experience in the diagnosis and management of patients with GD, including a review of pertinent literature. The availability of treatment, including enzyme therapy and substrate inhibition, has transformed the natural history of GD. However, there remains incomplete understanding of determinants of clinical outcome and critically, the basis of the increased propensity for PD and MM in a subset. Although biomarkers have been incorporated in the monitoring of patients, none have enabled prediction of disease course. The overarching goal of therapy is enhanced patient physical and functional well-being, achieved through the resolution of clinical problems and reduction in risks of disease-related complications. Early diagnosis and timely intervention logically enables the best prospects for the patient. The multiorgan involvement encountered in GD necessitates multidisciplinary care, ideally coordinated at centers of expertise.Expert opinion: The availability of therapeutic options has transformed the natural history of Gaucher disease, although the recognized increased risk of multiple myeloma and Parkinson disease in a subset of patients with type 1, and the devastating neurologic complications associated with type 2 and 3 disease, remain as hurdles that need to be overcome.