Olfactory Perception in Parkinson's Disease: The Impact of Variants (Sidransky Syndrome).

Parkinson's disease (PD) associated with 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 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), 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 ( < 0.001), particularly for leather, smoke, natural gas, pineapple, clove, rose, and lemon. Sidransky syndrome patients scored lower than iPD patients ( = 0.04). No significant olfactory deficits were observed in 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 carriers suggests that variants alone do not account for olfactory loss in PD. Hyposmia likely reflects broader PD pathology rather than a direct effect of the mutation.