Neurological evaluation of patients with Gaucher disease diagnosed as type 1

Abstract

Type 1 Gaucher disease (GD1) is characterised by lack of central nervous system involvement; however, there are several reports of associated neurological manifestations. The aim of this study was to systematically evaluate neurological manifestations in 31 patients with GD1 (12 males and 19 females; mean age 39.4 (range 5-77) years). Participants underwent a complete neurological examination and cognitive tests. Investigation of symptoms and medication intake, and motor and sensory electroneurograms were obtained. 30.7% of adult patients had neurological deficits, including psychomotor delay, parkinsonism, dementia, impaired saccadic ocular movements and peripheral nerve dysfunction. Three patients were redefined as type 3 GD. Electrodiagnosis was performed on 15 patients; 26.7% had reduced amplitude and/or abnormal waveforms in at least three nerves, 33.3% had a mild reduction in amplitude of two nerves and 40% had amplitude reduction in one nerve. Patients with three or more affected nerves had additional neurological symptoms. Our results demonstrate that neurological alterations occur in patients diagnosed with GD1, and subclinical peripheral neuropathy is a frequent finding.

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

“…Neurological manifestations of GD3 in juvenile patients are characterized by dysfunction of the major motor circuits, myoclonic epilepsy, oculomotor abnormalities and intellectual deterioration. The neurological abnormalities observed in our adult patients with GD1, and in recently published surveys, are predominantly parkinsonian symptoms and peripheral neuropathies (Halperin et al 2007;Hollak et al 2007;Capablo et al 2008;Cherin et al 2006). Thus, differences in the types of neurological dysfunction seen clinically, according to GD phenotype, suggest distinct neuropathologies within each GD phenotype.…”

“…A recent systematic investigation assessed neurological manifestations in 28 GD1 patients, 30.7% of whom had neurological deficits (Capablo et al 2008). The most frequent finding amongst these affected patients was subclinical peripheral neuropathy, as identified by electrophysiological examination in 40% of those who underwent this examination (n=15).…”

“…Some authors in small series have studied the relation between clinical and genetic characteristics (Chov et al 2007;Capablo et al 2008) in order to classified and ascribed neurological symptoms to type 3 GD. The genetic data of our large cohort do not allow this analysis knowing that the primary objective of the study was a clinical description with an estimation of prevalence of neurological manifestations in a large cohort of GD1 patients, and GD3 patients have been initially excluded.…”

Neuronopathic Forms in Subjects with Mutations in GBA Gene

“…As we mentioned before the N370S mutation has been traditionally associated with the absence of neurological disease; however, several studies reported a high proportion of patients with the N370S mutation were diagnosed with GD 1 and showed mild neurological symptoms such tremor, peripheral neuropathy, uncoordinated movements, and hearing loss (as well as Parkinson disease. (Capablo et al, 2008;Giraldo et al, 2011;Pastores et al, 2003). These findings are consistent with the recently established contention that the mutation could not fully protect the patient from the appearance of neurological symptoms (Halperin et al, 2007).…”

Glucocerebrosidase, a new player changing the old rules in Lewy body diseases

“…Although type 1 GD occurs in the general population, Ashkenazi Jews are more likely to contract type 1 GD (Hruska et al , 2008 ). While type 1 GD is considered non-neuropathic, a subset of patients show neurological symptoms such as parkinsonism, dementia, and subclinical peripheral neuropathy (Neudorfer et al , 1996 ;Biegstraaten et al , 2008 ;Capablo et al , 2008 ;Alonso -Canovas et al, 2010 ). Many studies have suggested a link between type 1 GD and Parkinson ' s disease (PD).…”