Gaucher Disease

Gaucher disease is the most common lysosomal storage disorder, caused by autosomal recessive mutations in the GBA gene affecting glucocerebrosidase enzyme activity. Without adequate enzyme function, glucocerebroside accumulates within macrophages throughout the body, creating characteristic "Gaucher cells." Type 1 disease (non-neuropathic, the most common form) manifests primarily with hepatosplenomegaly, bone disease, and hematologic abnormalities including anemia and thrombocytopenia, but typically does not affect the central nervous system. Patients experience debilitating bone pain, increased fracture risk, severe fatigue, and bleeding complications. Type 2 (acute neuronopathic) presents in infancy with severe neurological involvement and short survival. Type 3 (chronic neuronopathic) has neurological involvement with slower progression. Treatment options have revolutionized outcomes: enzyme replacement therapy (imiglucerase) and substrate reduction inhibitors (miglustat, eliglustat) can reverse many manifestations and prevent progression.