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
• glucocerebrosidase
• genotype/phenotype correlation
• enzyme replacement therapy
• substrate reduction therapy
• newborn screening
• parkinsonism
• chaperones
• biomarkers

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Institutes of Health