Polyneuropathy in Gaucher disease type 1 and 3 \u2013 a descriptive case series

Mattias Andréasson,Göran Solders,Cecilia K Björkvall,Per Svenningsson,Maciej Machaczka

doi:10.1038/s41598-019-51976-2

Abstract

Polyneuropathy (PNP) has been reported to be a possible phenotypic feature in Gaucher disease type 1 (GD1), while less is known about PNP in type 3 (GD3). We performed a cross-sectional study, exploring PNP in a Swedish GD cohort. Clinical assessment and blood biochemistry were carried out in 8 patients with GD1 and 11 patients with GD3. In patients with symptoms or clinical findings indicative of PNP, nerve conduction studies and quantitative sensory testing were performed. Assessments were compared to historic controls. A subclinical small fiber neuropathy (SFN) was demonstrated in 2 of 8 patients in the significantly (p = 0,021) older GD1 cohort. A large fiber PNP was evident in an additional 3 GD1 patients but could not be ascribed as disease manifestation. No GD3 patients exhibited neurophysiological evidence of small or large fiber PNP attributed to GD3. Compared to historic controls, no significant group differences were evident with regard to neuropathy rating scores. In summary, our study does not support large fiber PNP as a prevalent manifestation of GD. SFN is a possible feature in GD1, although small sample size limits definite conclusions. Our study provides novel data, arguing against clinically significant small or large fiber PNP in GD3.

Highlights

Polyneuropathy (PNP) has been reported to be a possible phenotypic feature in Gaucher disease type 1 (GD1), while less is known about PNP in type 3 (GD3)
The present study, comprising 8 GD1 and 11 GD type 3 (GD3) patients, demonstrated two cases interpreted as GD1 associated small fiber neuropathy (SFN) and no clear case of GD1 or GD3 associated large fiber PNP
In two GD1 patients with large fiber PNP (Pt 1, Pt 5), the underlying etiology was clouded by co-morbidities and the large fiber PNP found in the third GD1 patient (Pt 6) was confounded by exposure to miglustat

Summary

Introduction

Polyneuropathy (PNP) has been reported to be a possible phenotypic feature in Gaucher disease type 1 (GD1), while less is known about PNP in type 3 (GD3). Our study provides novel data, arguing against clinically significant small or large fiber PNP in GD3. GD type 1 (GD1) has historically been viewed as a non-neuropathic phenotype, mainly presenting with symptoms secondary to visceral involvement[2]. It is well-established that both homozygous and heterozygous GBA1 mutations confer an increased risk of developing Parkinson’s disease (PD)[4]. Retrospective, cross-sectional and prospective studies evaluating involvement of the peripheral nervous system (PNS) in GD1 have been conducted, showing an increased prevalence and incidence of polyneuropathy (PNP)[5,6,7]. An increased susceptibility to functional cobalamin deficiency in GD, precipitated by disease associated lysosomal dysfunction, has been suggested[12]

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Conclusion