Olfactory Perception in Parkinson’s Disease: The Impact of GBA1 Variants (Sidransky Syndrome)

Parkinson's disease (PD) associated with <i>GBA1</i> mutations-recently termed Sidransky syndrome-differs from idiopathic PD (iPD) by earlier onset, more rapid progression, and higher rates of non-motor symptoms. Our objective was to assess whether <i>GBA1</i> mutations contribute to olfactory dysfunction in PD and in asymptomatic carriers of the mutation. We compared olfactory and motor functions in 119 participants: Sidransky syndrome (n = 18), iPD (n = 30), <i>GBA1</i> variant carriers without PD (n = 21), Gaucher disease patients (n = 20), and healthy controls (n = 30). All were evaluated with the Brief Smell Identification Test (BSIT^®) and the motor part of the Movement Disorders Society Unified PD Rating Scale (MDS-mUPDRS). Mean age was 59.2 ± 11.7 years. Mean disease duration was 2.5 ± 2.2 years in Sidransky syndrome and 5.4 ± 4.9 years in iPD. We found that both PD groups had significantly lower BSIT^® scores than non-PD groups (<i>p</i> < 0.001), particularly for leather, smoke, natural gas, pineapple, clove, rose, and lemon. Sidransky syndrome patients scored lower than iPD patients (<i>p</i> = 0.04). No significant olfactory deficits were observed in <i>GBA1</i> carriers or Gaucher patients without PD. We conclude that hyposmia is more pronounced in Sidransky syndrome than in iPD. However, normal olfaction in non-parkinsonian <i>GBA1</i> carriers suggests that <i>GBA1</i> variants alone do not account for olfactory loss in PD. Hyposmia likely reflects broader PD pathology rather than a direct effect of the <i>GBA1</i> mutation.