Gaucher Disease and the Synucleinopathies

[摘要] Several recent observations suggest a connection between Gaucherdisease, the inherited deficiency of glucocerebrosidase, and thesynucleinopathies. Rare patients have been observed who developboth Gaucher disease and parkinsonism. Autopsy studies on thesesubjects reveal synuclein-positive Lewy bodies and inclusions. Anincreased incidence of synucleinopathies also has been noted inrelatives of Gaucher probands. In complementary studies, screeningof patients with parkinsonism has identified a greater thanexpected frequency of glucocerebrosidase mutations. Theseglucocerebrosidase mutation carriers have a wide spectrum ofassociated parkinsonian phenotypes, ranging from classicL-dopa-responsive Parkinson disease to a phenotypemore characteristic of Lewy body dementia. Despite thisassociation, the vast majority of Gaucher carriers and patientswith Gaucher disease never develop parkinsonism. However,mutations in this gene are likely to be a contributing risk factorin subjects otherwise prone to developing synucleinopathies.

[学科分类] 基础医学