Gaucher and Parkinson diseases

Over the last 4 years, increasing evidence has pointed to an unexpectedly close relationship between Gaucher disease (OMIM 606463) and Parkinson disease (PD) (OMIM 168600). Gaucher disease is a lysosomal storage disorder caused by mutations in the glucocerebrosidase gene leading to intracellular buildup of glucosylceramide. Although Gaucher disease is one of the classic, recessive disorders, the genotype–phenotype relationships for the disease are not clear and there is an enormous amount of unexplained phenotypic heterogeneity with some individuals having prominent spleen or liver symptoms and others having a neurodegenerative disease phenotype.¹ Although there have been brain neuropathologic examinations of persons dying of Gaucher disease, these have generally been of young patients and the occurrence of α-synuclein positive Lewy bodies (hallmark of PD) has only been assessed in a few elderly cases.²

One of the first hints that there might be a relationship between the two conditions came with the observation of PD in the relatives of individuals with Gaucher syndrome.^{3 …}