In rare cases where Parkinson’s disease occurs in Gaucher disease patients, mutations in the GBA gene — which cause Gaucher and are a risk factor for Parkinson’s — do not seem to accelerate the cognitive decline linked to the neurodegenerative disease, a small case study reports.
Gaucher disease is caused by mutations in the GBA gene, leading to insufficient production of the protein, glucocerebroside. As a result, patients accumulate a type of fat, or lipid, in several organs, including the liver, spleen, bone marrow, and nervous system, that impairs their normal functioning.
Mutations in the GBA gene are also important risk factors for sporadic, or non-familial, Parkinson’s disease. In fact, the link between the GBA gene and Parkinson’s was first recognized through clinical observation because Gaucher patients sometimes developed symptoms of Parkinsonism.
Researchers in this case series describe the cognitive features and progression of Parkinson’s disease in five patients with Gaucher disease who were followed for up to two years.
The five Gaucher disease patients developed the first symptoms of Parkinson’s disease — tremors and slowness of movement — between the ages of 48 and 67. This is much earlier than the age of onset for most Parkinson’s disease cases, which usually occurs around 70 years old.
“Other authors have similarly noted an earlier age of onset of PD [Parkinson’s disease] in patients with established GD [Gaucher disease],” the researchers wrote.
In three out of five patients, cognitive function was well-preserved, supporting previous reports showing that cognition in Gaucher disease patients is only slightly impaired even in later stages of the disease.
However, the findings also suggest that GBA mutations are not promoting a faster progression of Parkinson’s disease, the researchers noted.
Only two patients developed early cognitive deficits and dementia. One of them, a woman diagnosed with Parkinson’s at 67 years old, showed signs of significant cognitive impairment.
Previous studies have suggested that different mutations in the GBA gene may promote cognitive decline in patients with Parkinson’s disease, a manifestation researchers link to lower levels of glucocerebroside.
If GBA mutations were the causal explanation for accelerated Parkinson’s progression, “then one would expect patients with PD [Parkinson’s disease] in the context of established GD [Gaucher disease] to show consistent early decline of their cognitive powers. However, this is not necessarily the case,” the researchers wrote.
Overall, this small case study suggests that “GD mutations are not a reliable predictor of rapid progression to dementia in PD.”