The neurological manifestations of Gaucher disease type 1: the French Observatoire on Gaucher disease (FROG)

Abstract

These data challenge the current classification of GD, and suggest that the three forms of GD each involve a different profile of neurological manifestations.

Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study

“…No worsening has been evident for either patient on subsequent NCV tests, and both patients have remained asymptomatic with normal neurologic examinations after 3 years of treatment. Peripheral neuropathy, often subclinical, has been reported as a possible manifestation of GD1, as discussed by Cherin et al 14 Miglustat has been associated with symptomatic peripheral neuropathies and tremors that usually arise within the first few months and may lead to cessation of treatment. 13 In summary, the treatment responses observed during the first year of eliglustat tartrate therapy were confirmed and extended during the second year, as hematological, visceral, and skeletal manifestations of GD1 continued to improve.…”

The emergence of Parkinson disease among patients with Gaucher disease

“…In this cohort there was evidence of more severe Gaucher disease, as demonstrated by the greater presence of osteonecrosis in affected patients [27], leading to the speculation by the authors that "prolonged bouts of systemic inflammation … might accentuate the formation of alpha synuclein aggresomes in predisposed individuals". A French survey among Gaucher patients revealed 4% with Parkinson disease and 21% with at least one Parkinsonian/Parkinson-related sign/symptom [28].…”

Role of Lysosomal Enzymes in Parkinson’s Disease: Lesson from Gaucher’s Disease

“…Considering the spectrum of PD clinical manifestations in GD1 patients, a wide range of symptoms have been described, varying from the more aggressive, early-onset disease, with p o o r r e s p o n s e t o L -d o p a t h e r a p y , t o t h e more typical PD disease (presenting with asymmetric onset of resting tremor, bradykinesia, rigidity, gait and balance disturbance, weakness, pain, cognitive decline, and depression), responsive to L-dopa (Neudorfer et al, 1996;Tayebi et al, 2003;Bembi et al, 2003;Tayebi et al, 2001;Halperin et al 2006;Gan-Or et al, 2008;Bultron et al, 2010;Chérin et al, 2010;). The emerging evidence of the association between GBA mutations and a variety of synucleinopathyes may account for the wide phenotype variability (Hruska at al., 2006;Velayati et al, 2010).…”