Gaucher's disease: the changing paradigm of a lysosomal disorder

Area of Science:

• Biochemistry
• Genetics
• Oncology

Background:

• Gaucher's disease (GD) is the most prevalent lysosomal storage disorder, affecting approximately 1 in 50,000 individuals.
• It arises from a deficiency in the lysosomal enzyme beta-glucocerebrosidase, leading to glucosyl-ceramide accumulation in organs.

Purpose of the Study:

• To provide an overview of key milestones and treatments for Gaucher's disease.
• To highlight the disease's implications for understanding the pathogenesis of common conditions like Parkinson's disease and cancer.

Main Methods:

• Literature review of Gaucher's disease milestones and treatments.
• Analysis of the association between Gaucher's disease and increased cancer risk, including specific cancer types.
• Examination of the role of immunologic abnormalities and cytokine expression, such as interleukin-6.

Main Results:

• Substitutive enzymatic treatment for Gaucher's disease has been available for nearly two decades.
• Individuals with Gaucher's disease exhibit an elevated risk for cancers, particularly hepatobiliary and hematologic malignancies (multiple myeloma, B-cell neoplasms).
• This increased cancer risk is potentially linked to immunologic dysregulation and abnormal cytokine expression.

Conclusions:

• Gaucher's disease research offers insights into the pathogenesis of common diseases.
• Current and novel therapeutic strategies, including enzyme replacement and alternative/complementary options, are available globally.
• Understanding Gaucher's disease contributes to broader knowledge in lysosomal storage disorders, oncology, and neurodegenerative diseases.