Patients with a glucocerebrosidase gene (GBA) mutation have clinical deterioration consistent with the early stages of Parkinson's disease, according to a study published in JAMA Neurology.
Both patients with type 1 Gaucher disease and those with heterozygous GBA mutations displayed clinical deterioration consistent with the onset of Parkinson's disease, reported Michelle Beaven, MRCP, of the University College London, and colleagues.
A GBA mutation is the most important genetic risk factor for the development of Parkinson’s disease. The researchers sought to compare the development of the disease’s prodromal features in cohorts with and without a GBA mutation.
The study included 30 patients who had been diagnosed with Gaucher disease, 28 heterozygous GBA mutation carriers, and 26 genetically unrelated controls. The researchers assessed each patient over 2 years for clinical markers of Parkinson's disease, including hyposmia, rapid eye movement sleep behavior disorder, depression, autonomic dysfunction, cognitive function, and parkinsonian motor signs.
Depression scores were significantly worse for heterozygous carriers, and rapid eye movement sleep behavior disorder scores were significantly worse for patients with Gaucher disease. Both heterozygous carriers and patients with Gaucher disease had significantly increased parkinsonian motor signs. When the results from the heterozygous carriers and Gaucher disease patients were combined, they performed significantly worse on all included tests compared with controls.
These results indicate that as a group, patients with GBA mutations show deterioration consistent with the early onset of Parkinson's disease.
Numerically, the most important genetic risk factor for the development of Parkinson disease (PD) is the presence of a glucocerebrosidase gene (GBA) mutation.
The purpose of this study was to evaluate longitudinally and clinically a GBA mutation–positive cohort and the evolution of the prodromal features of PD.
This study indicates that, as a group, GBA mutation–positive individuals show a deterioration in clinical markers consistent with the prodrome of PD. Within this group of individual, 10% appear to be evolving at a more rapid rate.