scholarly journals Gaucher Disease and Cancer: Concept and Controversy

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Francis Y. M. Choy ◽  
Tessa N. Campbell
Keyword(s):  
Gaucher Disease ◽  
Wide Spectrum ◽  
Treatment Options ◽  
Substrate Reduction Therapy ◽  
Neurological Involvement ◽  
Enzyme Replacement ◽  
Skeletal Disease ◽  
Increased Risk ◽  
Risk Of Malignancy ◽  
Type 3

Gaucher disease is an inherited disorder caused by a deficiency in the lysosomal hydrolase glucocerebrosidase. There is a wide spectrum of clinical presentations, with the most common features being hepatosplenomegaly, skeletal disease, and cytopenia. Gaucher disease has been classified into three broad phenotypes based upon the presence or absence of neurological involvement: Type 1 (nonneuronopathic), Type 2 (acute neuronopathic), and Type 3 (subacute neuronopathic). The two main treatment options include enzyme replacement therapy and substrate reduction therapy. Recently, discussion has escalated around the association of Gaucher disease and cancer, with conflicting reports as to whether Gaucher patients have an increased risk of malignancy. In this review, we present both the concept and controversy surrounding the association of Gaucher disease with cancer.

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

2019 ◽  
Vol 103 (3) ◽  
pp. 315-326 ◽  
Author(s):  
Aaron W Winter ◽  
Ali Salimi ◽  
Luis H Ospina ◽  
Jonathan C P Roos
Keyword(s):  
Gaucher Disease ◽  
Substrate Reduction Therapy ◽  
Type I ◽  
Lysosomal Storage ◽  
Ocular Abnormalities ◽  
Enzyme Replacement ◽  
Ocular Manifestations ◽  
Ophthalmic Manifestations ◽  
Increased Risk ◽  
Risk Of Malignancy

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.

scholarly journals Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 69
Author(s):  
Aizeddin Mhanni ◽  
Michel Boutin ◽  
Frank Stockl ◽  
Janine Johnston ◽  
Jeff Barnes ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Visual Acuity ◽  
Gaucher Disease ◽  
Disease Type ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
High Concentration ◽  
Enzyme Replacement ◽  
Long Term Treatment ◽  
Type 3

Intraocular lesions have been infrequently reported in patients with Gaucher disease type 3 (GD3). We previously reported siblings with GD3 who responded well to the combination of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Here we report progressive bilateral vitreous and preretinal deposits with declining visual acuity requiring bilateral vitrectomies in one of these siblings. These ocular manifestations had progressed despite combined ERT and SRT with improvement in visual acuity after vitrectomies. Vitrectomy fluid analysis performed for the first time by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) identified a high concentration of glucosylceramide (GluCer) in the patient (262.842 nM) compared to a sample (0.428 nM from a patient without a lysosomal storage or known hereditary metabolic disorder). The GluCer detected in our patient was resolved into 12 different isoforms including two methylated ones. No evidence of galactosylceramide (GalCer) was detected. The development of these intraocular manifestations and their characterization by UPLC-MS/MS indicate a need for ongoing ophthalmologic evaluation of all GD patients and for new therapies that can cross the blood–retinal and blood–brain barriers for patients with GD and other neuropathic lysosomal storage disorders.

Potential efficacy of enzyme replacement and substrate reduction therapy in three siblings with Gaucher disease type III

2008 ◽  
Vol 31 (6) ◽  
pp. 745-752 ◽  
Author(s):  
J. Cox-Brinkman ◽  
M. J. van Breemen ◽  
B. T. van Maldegem ◽  
L. Bour ◽  
W. E. Donker ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Disease Type ◽  
Substrate Reduction Therapy ◽  
Type Iii ◽  
Enzyme Replacement ◽  
Substrate Reduction ◽  
Potential Efficacy

Gaucher Disease

2016 ◽  
Author(s):  
Carla E.M. Hollak
Keyword(s):  
Bone Disease ◽  
Gaucher Disease ◽  
Severe Disease ◽  
Substrate Reduction Therapy ◽  
Disease Treatment ◽  
Enzyme Replacement ◽  
Rare Cancers ◽  
Substrate Reduction ◽  
Associated Conditions

Gaucher disease is frequently diagnosed in adulthood and may manifest at any age. Chronic neuronopathic forms are rarely seen but may come to the attention of the adult physician. Nonneuronopathic or type 1 disease is extremely variable. Main symptoms are cytopenia, hepatosplenomegaly and bone disease. The majority of patients diagnosed in adulthood present with thrombocytopenia and splenomegaly. In moderate to severe disease, treatment with intravenous enzyme replacement is highly effective. Substrate reduction therapy with miglustat or eliglustat is an oral alternative for some. Awareness of a number of severe complications and associated conditions, including irreversible bone disease, rare cancers and Parkinson's disease, is of importance.

scholarly journals Optimization of Eliglustat-Based Glucosylceramide Synthase Inhibitors as Substrate Reduction Therapy for Gaucher Disease Type 3

2020 ◽  
Vol 11 (20) ◽  
pp. 3464-3473
Author(s):  
Michael W. Wilson ◽  
Liming Shu ◽  
Vania Hinkovska-Galcheva ◽  
Yafei Jin ◽  
Walajapet Rajeswaran ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Disease Type ◽  
Substrate Reduction Therapy ◽  
Glucosylceramide Synthase ◽  
Substrate Reduction ◽  
Type 3
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