Type 1 Gaucher’s Disease. Preliminary Data of an Homogeneous Neurological Study Performed in Spanish Patients.
Authors: Giraldo Pilar , Capablo Jose L. , Saez Alicia , Fraile Jesus , Alfonso Pilar , Pocovi Miguel , Giralt Manuel 
Published: April 2020

Background: Classically, type 1 Gaucher disease (GD) is characterized by organomegaly, haematological manifestations as anaemia and thrombocytopenia and frequent skeletal complications in absence of neurological manifestations. However, there is growing evidence for an association between GD and Parkinson’s disease and tremors, peripheral neuronopathy and others. These manifestations recently have been described in type 1 GD patients. The aim of our study has been to evaluate systematically a group of type 1 GD patients in order to assess about the presence of neurological manifestations.

Design and methods: In this study, we have included 21 type 1 GD Spanish patients in follow-up for five years or more (male 7/female 14; mean age at diagnosis 24±16.88 years; SSI 6.5±3.2; genotype N370S or G377S heterozygous) 7 patient under enzyme replacement therapy (ERT) every two weeks at mean dose of 45 U/kg for ten years or more, 5 received therapy since four years ago and 4 under ERT since three years ago, all of them with satisfactory response (reduction in visceral size and normalization of hematological parameters). Five patients had not received any pharmacological therapy. All patients accept to participate in the study and the neurological exam and neurophysiological tests were performed by the same specialists. The protocol included a detailed inquiry about symptoms and concomitant medications and a neurological exam by a modified total neuropathy score to determine neurological signs. A superficial electroneurogram in sural and peroneal nerve was performed. As a cognoscenti test we used the memory impairment screen for dementia.

Results: From a total of 21 patients, 8 patients (38.09%) showed some neurological deficits: a 8 years old child (GBA genotype G377S/R463C) develop ocular alteration and psychomotor delayed and he was reclassified as type 3 GD patient; two females siblings of 64 and 61 years old (GBA genotype N370S/IVS4-2A&gt;G +c.( −203)A&gt;G) has evident neurological symptoms. One of them presented parkinsonism since 40 years old and she did not response favourably to treatment with L-Dopa. The other sister carrier a joint hip replacement, has been under ERT since 1994 and she has developed dementia and Parkinson’s disease at 68 years old. Another splenectomized patient (age at diagnosis: 15 years, genotype N370S/L444P) was classified with mild or moderate and stable disease without ERT the neurological exam showed saccades ocular movements. One male 25 years old (genotype N370S/N370S) has been under ERT three years ago and presents abnormalities of eye movement. A 32 years old woman, (genotype N370S/L444P) had peripheral neuronopathy in arms. A 17 years old woman (genotype N370S heterozygous) had clonic movements in upper extremities. A child 3.5 years old (genotype N370S heterozygous) had psycomotor incordination.

Comments: Due to the high incidence of neurological complaints in patients with GD type 1 it is necessary a precise and detailed clinical study to discard concurrent and medical problems and/or side effects from concomitant medications or true neurological problems related to GD.