The definition of neuronopathic Gaucher disease

Abstract

Neuronopathic Gaucher disease (nGD) has a very wide clinical and genotypic spectrum. However, there is no consensus definition of nGD, including no description of how best to diagnostically separate the acute form—Gaucher type 2—from the subacute or chronic form—Gaucher type 3. In this article, we define the various forms of Gaucher disease with particular emphasis on the presence of gaze palsy in all patients with nGD. This consensus definition will help in both clinical diagnosis and appropriate patient recruitment to upcoming clinical trials.

The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

“…Adultonset Parkinsonism may occur in patients with type 1 GD [1,2]. However, Parkinsonism is not considered as a feature of neuronopathic GD; rather, GBA mutations are one of the risk factors of Parkinsonism [3].…”

“…According to the International Collaborative Gaucher Group's Gaucher Registry (clinicaltrials.gov NCT00358943), ~94% of patients in Western countries are of the non-neuronopathic type, whereas half of the patients in Japan, Korea, and China are classi ed as the neuronopathic type [4]. Common mutations including c.1226A>G (p.N409S), c.1448T>C (p.L483P), c.115+1G>A (IVS2+1), and c.84dupG (p.L29Afs*18), account for 90% of all mutations in the Jewish population and 50% of all mutations in the non-Jewish populations [3,6,7]. Among these, the most prevalent mutation among Caucasians is p.N409S, which accounts for approximately 80% of mutations [8].…”

The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

“…Adult-onset Parkinsonism may occur in patients with type 1 GD [1,2]. However, Parkinsonism is not considered as a feature of neuronopathic GD; rather, GBA mutations are one of the risk factors of Parkinsonism [3].…”

“…According to the International Collaborative Gaucher Group's Gaucher Registry (clinicaltrials.gov NCT00358943), ~ 94% of patients in Western countries are of the non-neuronopathic type, whereas, half of the patients in Japan, Korea, and China are classi ed as the neuronopathic type [4]. Common mutations including p.N409S, p.L483P, c.115 + 1G > A, and c.84dupGG, account for 90% of the Jewish population and 50% of non-Jewish populations [3,5,6]. Among these, the most prevalent mutation among Caucasians is p.N409S, which accounts for approximately 80% of mutations [7].…”

“…Among these, the most prevalent mutation among Caucasians is p.N409S, which accounts for approximately 80% of mutations [7]. GD patients harbouring a p.N409S mutation even in one allele can be excluded from a diagnosis of neuronopathic GD (type 2 or 3) [3], suggesting that the mutation may exert a neuroprotective effect [3,[5][6][7]. However, the p.N409S mutation has been rarely identi ed among Asian GD patients, particularly among Japanese and Korean patients [4,7,8].…”