Parkinsonism in Gaucher's disease type 1: Ten new cases and a review of the literature

Kraoua, Ichraf; Stirnemann, Jérôme; Ribeiro, Maria João; Rouaud, Tiphaine; Vérin, Marc; Annic, Agnès; Rosé, Christian; Defebvre, Luc; Remenieras, Liliane; Schüpbach, Michaël; Belmatoug, Nadia; Vidailhet, Marie; Sedel, Frédéric

doi:10.1002/mds.22593

Cited by 28 publications

(22 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These patients may benefit from dopamine therapies used for PD whereas enzyme replacement and substrate reduction therapy are ineffective on GD-associated parkinsonism 60. Further, optical coherence tomography (OCT) demonstrated thinning of the retinal ganglion cell layer in GD patients (Type-I) and carriers who manifested clinical markers of early neurodegeneration (cognitive impairment and hyposmia) 14.…”

Section: Discussionmentioning

confidence: 99%

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

et al. 2019

View full text Add to dashboard Cite

Gaucher disease (GD) results from a deficiency of glucocerebrosidase activity and the subsequent accumulation of the enzyme’s metabolites, principally glucosylsphingosine and glucosylceramide. There are three principal forms: Type I, which is the most common, is usually considered non-neuronopathic. Type II, III and IIIc manifest earlier and have neurological sequelae due to markedly reduced enzyme activity. Gaucher’s can be associated with ophthalmological sequelae but these have not been systematically reviewed. We therefore performed a comprehensive literature review of all such ophthalmic abnormalities associated with the different types of Gaucher disease. We systematically searched the literature (1950 – present) for functional and structural ocular abnormalities arising in patients with Gaucher disease and found that all subtypes can be associated with ophthalmic abnormalities; these range from recently described intraocular lesions to disease involving the adnexae, peripheral nerves and brain. In summary, Gaucher can affect most parts of the eye. Rarely is it sight-threatening; some but not all manifestations are amenable to treatment, including with enzyme replacement and substrate reduction therapy. Retinal involvement is rare but patients with ocular manifestations should be monitored and treated early to reduce the risk of progression and further complications. As Gaucher disease is also associated with Parkinsons disease and may also confer an increased risk of malignancy (particularly haematological forms and melanoma), any ocular abnormalities should be fully investigated to exclude these potential underlying conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

et al. 2019

View full text Add to dashboard Cite

show abstract

“…[ 11 C]-CFT PET has demonstrated decreased uptake suggestive of presynaptic dopaminergic dysfunction in GBA heterozygotes and homozygotes with parkinsonism, 54, 55 but normal uptake in asymptomatic GBA carriers 54 . F-fluorodopa PET, which evaluates presynaptic dopamine terminals, has demonstrated reduced f-dopa uptake in the striatum of GD1 patients 4, 56 and GBA-PD heterozygotes 52 , similar to IPD. Fluorodeoxyglucose (FDG) PET has shown hypermetabolism in the lentiform nuclei in GD1-PD patients, similar to IPD 4 .…”

Section: Neuroimaging In Gba-pdmentioning

confidence: 97%

The Association Between ß-Glucocerebrosidase Mutations and Parkinsonism

Swan

Saunders‐Pullman

2013

Curr Neurol Neurosci Rep

View full text Add to dashboard Cite

Mutations in the ß-glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme ß-glucocerebrosidase, have traditionally been implicated in Gaucher disease, an autosomal-recessive lyososomal storage disorder. Yet the past two decades have yielded an explosion of epidemiological and basic-science evidence linking mutations in GBA with the development of Parkinson disease as well. Although the specific contribution of mutant GBA to the pathogenesis of parkinsonism remains unknown, evidence suggests both loss of function and toxic gain-of-function by abnormal ß-glucocerebrosidase may be important, and a close relationship between ß-glucocerebrosidase and α-synuclein. Furthermore, multiple lines of evidence suggest that while GBA-associated PD closely mimics idiopathic PD (IPD), it may present at a younger age, and is more frequently complicated by cognitive dysfunction. Understanding the clinical association between GBA and PD, and the relationship between ß-glucocerebrosidase and α-synuclein, may enhance understanding of the pathogenesis of IPD, improve prognostication and treatment of GBA carriers with parkinsonism, and may furthermore inform therapies for IPD not due to GBA mutations.

show abstract

“…However, neurological symptoms including peripheral neuropathy and Parkinsonism have increasingly been reported in systematic studies of patientswithGD1 [6–10]. Additionally, several case reports of patientswithGD1 developing Parkinsonism have been published [11–17]. Other studies in patients with known Parkinson's disease demonstrated an association with mutations in the GBA gene [15,18–22].…”

Section: Introductionmentioning

confidence: 99%

The incidence of Parkinsonism in patients with type 1 Gaucher disease: Data from the ICGG Gaucher Registry

Rosenbloom

Balwani

Bronstein

et al. 2011

Blood Cells, Molecules, and Diseases

132

110

View full text Add to dashboard Cite

Purpose Investigate the incidence of Parkinsonism among patients with Gaucher disease type 1 (GD1) and describe demographics, genotypes, and Gaucher disease (GD)-related characteristics for affected and non-affected patients. Methods Study type: Cohort study with age- and gender-matched nested case–control analysis. Calculation of event incidence, standardized morbidity ratio, and event-free survival (Kaplan–Meier). Data source: The International Collaborative Gaucher Group (ICGG) Gaucher Registry data as of June 2010. Study cohort: GD1 patients with any report of Parkinsonism. Pre-matching control group: All GD1 patients with no report of Parkinsonism. Results The matched study cohort comprised of 68 patients with reports of Parkinsonism and 649 patients without Parkinsonism. Demographic and clinical characteristics suggest a milder GD phenotype in patients with Parkinsonism compared to the control group. The most prevalent GD1 genotype was N370S/N370S (39% for controls; 46% for patients with Parkinsonism). Patients with Parkinsonism were diagnosed with GD1 at a mean age of 37 years compared to 31 years in control patients. The standardized morbidity ratio for the development of Parkinsonism among all GD1 patients indicated an approximately 6 to 17 fold increase over that of 2 reference populations. The mean age of reported Parkinsonism onset was 57 years compared to 60 years in the general population (Lees, Hardy, and Revesz, 2009 [1]). The probability that a patient with GD1 will develop Parkinsonism before age 70 years is 5 to 7% and 9 to 12% before age 80 years. Conclusions The incidence of Parkinsonism among GD1 patients is significantly increased compared to two reference populations. GD1 patients with Parkinsonism have a later median age at GD diagnosis, later age at the start of treatment, and later age at death than patients with GD1 alone. The Gaucher-related clinical profile of GD1 patients with Parkinsonism is similar to or milder than the GD1 alone group. Therefore, severity of the common GD1 clinical manifestations does not appear to be predictive for the onset of Parkinsonism.

show abstract

Parkinsonism in Gaucher's disease type 1: Ten new cases and a review of the literature

Cited by 28 publications

References 28 publications

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

The Association Between ß-Glucocerebrosidase Mutations and Parkinsonism

The incidence of Parkinsonism in patients with type 1 Gaucher disease: Data from the ICGG Gaucher Registry

Contact Info

Product

Resources

About