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

TL;DR

This study finds that Parkinson’s disease linked to GBA1 mutations (Sidransky syndrome) shows more severe smell loss than typical Parkinson’s, but GBA1 mutations alone don’t cause smell loss without Parkinson’s.

Contribution

The study is the first to compare olfactory dysfunction in Sidransky syndrome versus idiopathic Parkinson’s disease and non-PD GBA1 carriers.

Findings

Sidransky syndrome patients had significantly lower smell test scores than idiopathic PD patients.

GBA1 carriers without Parkinson’s disease showed no olfactory deficits.

Hyposmia in Sidransky syndrome likely reflects broader PD pathology, not the GBA1 mutation alone.

Abstract

Parkinson’s disease (PD) associated with GBA1 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 GBA1 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), GBA1 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 (p < 0.001), particularly for leather, smoke, natural gas, pineapple, clove, rose, and lemon. Sidransky syndrome patients scored lower than iPD patients (p = 0.04). No significant olfactory deficits were observed in GBA1 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 GBA1 carriers suggests that GBA1 variants alone do not account for olfactory loss in PD. Hyposmia likely reflects broader PD pathology rather than a direct effect of the GBA1 mutation.

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