Glucocerebrosidase mutations and phenoconversion of REM sleep behavior disorder to parkinsonism and dementia

Mutations in the glucocerebrosidase (GBA) gene are strongly associated with REM sleep behavior disorder (RBD). It is unclear whether GBA mutations might affect clinical phenotype or rate of phenoconversion to parkinsonism or dementia.

We sequenced GBA in polysomnographic-proven idiopathic RBD (iRBD) patients. The effect of GBA mutations on clinical neurodegenerative markers and phenoconversion rate was assessed.

Of 102 patients sequenced, 13 (13%) had GBA mutations and 89 did not. Aside from lower self-reported age of RBD onset in subjects with GBA mutations, no significant differences were observed in any clinical marker between patients with and without mutations. However, GBA mutations were associated with 3.2-fold higher phenoconversion rate from RBD to parkinsonism and/or dementia (95% CI = 1.4-7.3, p = 0.006).

Although GBA mutations do not appear to affect clinical neurodegenerative markers (and thus are not differentiable as an independent subtype of iRBD), they may accelerate the conversion of RBD to defined neurodegenerative synucleinopathy.