Gaucher Disease Unveiled: From Genes to Targeted Therapy

Gaucher disease (GD), an autosomal recessive lysosomal storage disorder first described by Philippe Gaucher in 1882, results from mutations in the GBA1 gene, leading to deficient glucocerebrosidase activity and subsequent accumulation of glucocerebroside in macrophages. This causes multisystem involvement, primarily affecting the liver, spleen, and bone marrow. With an incidence of 1:40,000-60,000 globally, GD shows ethnic variability, being more prevalent among Ashkenazi Jews (1:850). Type 1 (nonneuronopathic) accounts for 90% of cases, while types 2 and 3 (neuronopathic) and rare perinatal/cardiovascular forms present with severe neurological or systemic complications. Diagnosis relies on leukocyte enzyme assay (<15% activity), GBA1 genetic testing, elevated biomarkers (chitotriosidase, glucosylsphingosine), and imaging (MRI, ultrasound). Treatment includes enzyme replacement therapy (imiglucerase, velaglucerase alfa), substrate reduction therapy (eliglustat, miglustat), and supportive care, with emerging options like gene therapy. Despite treatment, patients face complications such as bone disease, Parkinsonism (5-8% risk), and hematologic abnormalities, necessitating lifelong multidisciplinary monitoring. Early diagnosis and tailored therapy significantly improve outcomes, though neuronopathic forms remain challenging to manage.