GBA

About GBA

GBA, now officially named GBA1, on chromosome 1q22 encodes glucocerebrosidase, a lysosomal enzyme that breaks down the lipid glucosylceramide. Variants on both copies cause Gaucher disease, the most common lysosomal storage disorder, which is especially frequent among Ashkenazi Jewish people. Lipid laden macrophages, called Gaucher cells, accumulate in the spleen, liver, and bone marrow. Type 1, the non neuronopathic and most common form, causes enlargement of the spleen and liver, anemia, low platelets, bone pain and bone crises, and sometimes lung disease. Type 2 is an acute neuronopathic form that is fatal in infancy, and type 3 is a chronic neuronopathic form with variable severity. The disease is named after the French physician Philippe Gaucher, who described it in 1882. Enzyme replacement therapies, including imiglucerase, velaglucerase, and taliglucerase, transformed the outlook for type 1, and substrate reduction therapies such as eliglustat and miglustat are oral alternatives. Carrying a single GBA1 variant is one of the most important genetic risk factors for Parkinson disease and dementia with Lewy bodies, and GBA1 associated Parkinson disease tends to show earlier onset and more cognitive involvement, highlighting the role of lysosomal dysfunction in neurodegeneration.