Gaucher Disease: Genetics, Types, and Treatment Landscape

Gaucher disease is an autosomal recessive lysosomal storage disorder from GBA mutations → deficient glucocerebrosidase → glucosylceramide accumulation in macrophages (Gaucher cells).

Three Types

• Type 1 (non‑neuronopathic, 90%): Hepatosplenomegaly, cytopenias, bone disease (osteonecrosis, fractures), fatigue. No primary CNS involvement. Normal lifespan with treatment.
• Type 2 (acute neuronopathic): Onset <6 months; severe neurodegeneration (brainstem), stridor, swallowing difficulty, death by age 2–3.
• Type 3 (subacute neuronopathic): Later onset; progressive neurological decline (myoclonus, seizures, dementia) plus visceral involvement. Survival into adulthood.

Therapies

• Enzyme replacement therapy (ERT): Imiglucerase, velaglucerase, taliglucerase (IV q2 weeks) – reverses visceral/hematologic/bone manifestations in Type 1/3.
• Substrate reduction therapy (SRT): Eliglustat, miglustat (oral) – reduces glucosylceramide synthesis. For Type 1.
• Supportive: bisphosphonates, joint replacement, splenectomy (rare now).

Genetic counseling for families; carrier screening in Ashkenazi Jewish population (1:15 carrier frequency).