For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
25
views
37
references
 Top references
cited by
4
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      395
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Eye Movement Impairment Recovery in a Gaucher Patient Treated with Miglustat

      other

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In Gaucher Disease (GD) the enzyme (imiglucerase) replacement therapy (ERT) is not able to stop the progression of the neurological involvement, while the substrate reduction therapy (SRT), performed by N-Butyldeoxynojirimycin (miglustat), is an alternative that should be evaluated. Two sisters, presenting the same genotype (R353G/R353G), were diagnosed as suffering from GD; one of them later developed neurological alterations identified by quantitative saccadic eye movements analysis. The aim of the study was to quantitatively measure the miglustat effects in this GD neurological patient. Eye movement analysis during subsequent controls was performed by estimating the characteristic parameters of saccadic main sequence. The study demonstrates that the SRT alone can be effective in GD3. Moreover, it confirms that quantitative eye movement analysis is able to precociously identify also slight neurological alterations, permitting more accurate GD classification.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis.

          Timothy Cox, Robin Lachmann, Carla EM Hollak … (2000)
          Current treatment for Gaucher's disease involves administration of intravenous glucocerebrosidase to degrade glucocerebroside stored in lysosomes. Lowering the rate of biosynthesis of glucocerebroside should decrease accumulation of this substrate. We investigated the safety and efficacy of OGT 918 (N-butyldeoxynojirimycin), an inhibitor of glucosyltransferase, as a novel oral treatment for non-neuronopathic Gaucher's disease. We recruited, into a 1-year open-label study, 28 adults (seven with previous splenectomies) from four national Gaucher's referral clinics, who were unable or unwilling to receive enzyme treatment. We measured liver and spleen volume by computed tomography or magnetic resonance imaging at baseline and at months 6 and 12, and biochemical and haematological variables monthly, including chitotriosidase activity (a sensitive marker of Gaucher's disease activity). Patients were started on 100 mg oral OGT 918 three times daily. Baseline liver volumes were 1.1-2.7 times normal and spleen volumes 5.1-24.8 times normal. At 12 months, mean liver and spleen volumes were significantly lowered by 12% (95% CI 7.8-16.4) and 19% (14.3-23.7), respectively (each p<0.001). Haematological variables improved slightly. Mean organ volume and blood counts improved continually between 6 months and 12 months of treatment. Mean chitotriosidase concentrations fell by 16.4% over 12 months (p<.0001). Six patients withdrew because of gastrointestinal complaints (two), personal reasons (two), or severe pre-existing disease (two). The most frequent adverse effect was diarrhoea, which occurred in 79% of patients shortly after the start of treatment. Decrease of substrate formation by OGT 918 improves key clinical features of non-neuronopathic Gaucher's disease. The strategy justifies further trials in this and other glycosphingolipid storage disorders.
          Article 0 comments Cited 110 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Gaucher disease: complexity in a "simple" disorder.

            Ellen Sidransky (2015)
            Gaucher disease, the recessively inherited deficiency of the enzyme glucocerebrosidase and the most common sphingolipidosis, has both non-neurological and neuronopathic forms and a continuum of diverse clinical manifestations. Studies of genotype-phenotype correlations reveal significant genotypic heterogeneity among clinically similar patients, and vastly different phenotypes among patients with the same mutations. The region surrounding the glucocerebrosidase gene (GBA) on chromosome 1q is particularly gene-rich, with a highly homologous pseudogene sequence 16 kb downstream. Recombination events within the GBA locus contribute to the etiology of some mutations in Gaucher disease. Studies of patients with Gaucher disease and atypical manifestations, including parkinsonism, myoclonic epilepsy, cardiac involvement and collodion skin, seek to define other genetic or environmental factors contributing to the phenotypes. Recent reports demonstrating an association between Gaucher disease and parkinsonism provide an example of heterozygosity for a Mendelian disorder acting as a risk factor for a complex disease. There are rare patients with Gaucher disease and differing genotypes who develop early onset, treatment-refractory parkinsonism. Neuropathology in a group of these patients showed alpha-synuclein-reactive Lewy bodies in brain regions specifically associated with Gaucher disease. Family studies of these probands suggested that the incidence of parkinsonism might be more frequent in obligate heterozygotes. In a complementary finding, the examination of GBA in autopsy samples from individuals with sporadic Parkinson disease identified alterations in the GBA sequence in 14% of the cohort. These studies provide evidence that altered glucocerebrosidase may contribute to a vulnerability to parkinsonism. Moreover, this research demonstrates how insights from rare, single gene disorders like Gaucher disease can provide a window into the etiology of more common, multifactorial genetic diseases.
            Article 0 comments Cited 97 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry.

              Neal J. Weinreb, Joel Charrow, Hans Andersson … (2002)
              Gaucher disease is the first lysosomal storage disorder to be treated with macrophage-targeted enzyme replacement therapy. Previous studies in relatively small numbers of patients demonstrated short-term efficacy of this treatment. This study describes the effects of 2 to 5 years of treatment on specific manifestations of type 1 Gaucher disease. Physicians reported data from 1028 patients to the Gaucher Registry. Assessment of response included serial measurements of hemoglobin concentration, platelet count, liver and spleen volumes, and the occurrence of bone pain and bone crises. Among anemic patients, hemoglobin concentration increased to normal or near normal within 6 to 12 months, with a sustained response through 5 years. In thrombocytopenic patients with intact spleens, the most rapid response occurred during the first 2 years, with slower improvement thereafter. The likelihood of achieving a normal platelet count decreased with increasing severity of baseline thrombocytopenia. In patients who had undergone splenectomy, platelet counts returned to normal within 6 to 12 months. Hepatomegaly decreased by 30% to 40% during follow-up; splenomegaly decreased 50% to 60%, but rarely to volumes below five times normal size. In patients with pretreatment bone pain or bone crises, 52% (67/128) were pain free after 2 years and 94% (48/51) reported no additional crises. Enzyme replacement therapy prevents progressive manifestations of Gaucher disease, and ameliorates Gaucher disease-associated anemia, thrombocytopenia, organomegaly, bone pain, and bone crises.
              Article 0 comments Cited 92 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Neurol Res Int
                Journal ID (publisher-id): NRI
                Title: Neurology Research International
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2090-1852
                ISSN (Electronic): 2090-1860
                Publication date (Print): 2010
                Publication date (Electronic): 26 September 2010
                Volume: 2010
                Electronic Location Identifier: 358534
                Affiliations
                1Department of Electronics (DEEI), University of Trieste, 34127 Trieste, Italy
                2Department of Ophthalmology, IRCCS “Burlo Garofolo”, 34137 Trieste, Italy
                3Metabolic Diseases Unit, IRCCS “Burlo Garofolo”, 34137 Trieste, Italy
                Author notes

                Academic Editor: Dirk Deleu

                Article
                DOI: 10.1155/2010/358534
                PMC ID: 2989716
                PubMed ID: 21152212
                SO-VID: cb04db48-715e-4584-b683-87bf416cb430
                Copyright © Copyright © 2010 Agostino Accardo et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 22 March 2010
                Date revision received : 6 July 2010
                Date accepted : 8 September 2010
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Neurology
                Data availability:
                ScienceOpen disciplines: Neurology

                Comments

                Comment on this article

                scite_

                Similar content395

                See all similar

                Cited by4

                See all cited by

                Most referenced authors191

                See all reference authors