Patients with Gaucher Disease and Parkinsonism Show Variation in Clinical Symptoms, Study Shows

Patients with Gaucher Disease and Parkinsonism Show Variation in Clinical Symptoms, Study Shows

GBA1 mutations underlying Gaucher disease are not a good prognostic factor for the likelihood of patients developing Parkinson’s disease, according to the results of the study “Clinical course and prognosis in patients with Gaucher disease and parkinsonism,” published in the journal Neurology Genetics.

A small fraction of patients with Gaucher disease, caused by mutations in the glucocerebrosidase (GBA1) gene, ultimately develop Parkinson’s. As a result, despite affecting a low number of patients, investigating the causes underlying the association between both diseases may help patients’ prognosis.

In this new research, researchers performed a retrospective observational study conducted with 19 patients with Gaucher disease and parkinsonism. Patients were enrolled at the Clinical Center of the National Institutes of Health (NIH) in Bethesda, Maryland, and followed over 10 years. Disease severity was determined by analyzing a complex and wide series of parameters, including physical, neurologic, pathologic, and neurocognitive examinations; family histories, imaging analysis, olfactory testing, and validated questionnaires.

Researchers observed that, in general, this cohort of Gaucher patients with GBA1 mutations exhibited earlier age at onset of Parkinson’s disease symptoms, as well as evidence of mild cognitive dysfunction (mean age of 49.7 years, compared to 62.4 years and 54.9 years in patients with idiopathic Parkinson’s disease and in GBA1 heterozygotes with Parkinson’s disease, respectively).

Some patients in the cohort, despite small exhibited heterogeneity, showed a clinical course similar to that of idiopathic Parkinson’s disease (the most common type of parkinsonism and where the cause for disease is not known). Others exhibited features characteristic of dementia with Lewy bodies (a disease where patients commonly experience visual hallucinations and also have some Parkinson’s-type symptoms, such as slowness of movement, stiffness and tremor). Notably, when the team examined patients as a group they found no uniformly aggressive form of parkinsonism after the first wave of symptoms.

In conclusion, these results show a marked clinical variation in this cohort of patients with Gaucher disease and parkinsonism, with a fraction of patients showing early onset and prominent cognitive changes, while others showing a slower clinical course.

Therefore, GBA1 mutations are likely not a reliable prognostic indicator in Parkinson’s disease in clinical settings. Researchers highlight that future studies with patients with both Gaucher disease and parkinsonism are important for our understanding of the relationship between both disorders.