Recent advances in the diagnosis and management of Gaucher disease

Abstract

Introduction: Gaucher disease, the autosomal recessive deficiency of the lysosomal enzyme glucocerebrosidase, is associated with wide phenotypic diversity including non-neuronopathic, acute neuronopathic, and chronic neuronopathic forms. Overlap between types can render definitive diagnoses difficult. However, differentiating between the different phenotypes is essential due to the vast differences in clinical outcomes and response to therapy. Genotypic information is helpful, but cannot always be used to make clinical predictions. Current treatments for Gaucher disease, including enzyme replacement therapy and substrate reduction therapy, can reverse many of the non-neurological manifestations, but these therapies must be administered continually and are extremely costly.

Areas covered: We reviewed the literature concerning the varied clinical presentations of Gaucher disease throughout the lifetime, along with treatment options, management goals, and current and future research challenges. A PubMed literature search was performed for relevant publications between 1991 to January 2018.

Expert commentary: Interest and research in the field of Gaucher disease is rapidly expanding. However, significant barriers remain in our ability to predict phenotype, assess disease progression using objective biomarkers, and determine optimal treatment strategy on an individual basis. As the field grows, we anticipate identification of genetic modifiers, new biomarkers, and small-molecule chaperone therapies, which may improve patient quality of life.

Keywords: Gaucher disease; biomarkers; chaperones; enzyme replacement therapy; genotype/phenotype correlation; glucocerebrosidase; newborn screening; parkinsonism; substrate reduction therapy.

Figure 1.

Photo of an 14-month-old child with hepatosplenomegaly and growth delay, recently diagnosed with Gaucher disease. Because he presented in the first year of life, his parents were initially told that he had type 2 Gaucher disease. While this is clearly not the case, it has been challenging to determine whether he has type 1 or type 3 Gaucher disease. He currently demonstrates no neurological features, yet his genotype is L444P/L444P. Picture with written parent consent.