gaucher disease

Summary

Summary: An autosomal recessive disorder caused by a deficiency of acid beta-glucosidase (GLUCOSYLCERAMIDASE) leading to intralysosomal accumulation of glycosylceramide mainly in cells of the MONONUCLEAR PHAGOCYTE SYSTEM. The characteristic Gaucher cells, glycosphingolipid-filled HISTIOCYTES, displace normal cells in BONE MARROW and visceral organs causing skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement.

Top Publications

  1. Marugan J, Zheng W, Motabar O, Southall N, Goldin E, Westbroek W, et al. Evaluation of quinazoline analogues as glucocerebrosidase inhibitors with chaperone activity. J Med Chem. 2011;54:1033-58 pubmed publisher
    b>Gaucher disease is a lysosomal storage disorder (LSD) caused by deficiency in the enzyme glucocerebrosidase (GC)...
  2. Wang F, Agnello G, Sotolongo N, Segatori L. Ca2+ homeostasis modulation enhances the amenability of L444P glucosylcerebrosidase to proteostasis regulation in patient-derived fibroblasts. ACS Chem Biol. 2011;6:158-68 pubmed publisher
  3. Balwani M, Fuerstman L, Kornreich R, Edelmann L, Desnick R. Type 1 Gaucher disease: significant disease manifestations in "asymptomatic" homozygotes. Arch Intern Med. 2010;170:1463-9 pubmed publisher
    Type 1 Gaucher disease (GD), an autosomal recessive lysosomal storage disease, is most prevalent in the Ashkenazi Jewish (AJ) population...
  4. Goldin E. Gaucher disease and parkinsonism, a molecular link theory. Mol Genet Metab. 2010;101:307-10 pubmed publisher
    ..Both hypotheses are not sufficient to explain the linkage. In order to develop a more inclusive theory we introduced into the model the prion theory and the second hit. Other possibilities are also brought into consideration. ..
  5. Ong D, Mu T, Palmer A, Kelly J. Endoplasmic reticulum Ca2+ increases enhance mutant glucocerebrosidase proteostasis. Nat Chem Biol. 2010;6:424-32 pubmed publisher
  6. Sun Y, Ran H, Liou B, Quinn B, Zamzow M, Zhang W, et al. Isofagomine in vivo effects in a neuronopathic Gaucher disease mouse. PLoS ONE. 2011;6:e19037 pubmed publisher
    ..enhances acid ?-glucosidase (GCase) function by altering folding, trafficking, and activity in wild-type and Gaucher disease fibroblasts...
  7. McNeill A, Roberti G, Lascaratos G, Hughes D, Mehta A, Garway Heath D, et al. Retinal thinning in Gaucher disease patients and carriers: results of a pilot study. Mol Genet Metab. 2013;109:221-3 pubmed publisher
    Both Gaucher disease patients and heterozygous glucocerebrosidase mutation carriers are at increased risk of Parkinson's disease. Retinal thinning has been reported in early Parkinson's disease...
  8. Ron I, Rapaport D, Horowitz M. Interaction between parkin and mutant glucocerebrosidase variants: a possible link between Parkinson disease and Gaucher disease. Hum Mol Genet. 2010;19:3771-81 pubmed publisher
    b>Gaucher disease (GD), a sphingolipidosis characterized by impaired activity of the lysosomal enzyme glucocerebrosidase (GCase), results from mutations in the GCase-encoding gene, GBA...
  9. Suzuki Y. Chaperone therapy update: Fabry disease, GM1-gangliosidosis and Gaucher disease. Brain Dev. 2013;35:515-23 pubmed publisher
    ..GM1-gangliosidosis and Morquio B disease) and ?-glucosidase deficiency disorders (phenotypic variations of Gaucher disease), respectively...

More Information

Publications99

  1. Lo S, Liu J, Chen F, Pastores G, Knowles J, Boxer M, et al. Pulmonary vascular disease in Gaucher disease: clinical spectrum, determinants of phenotype and long-term outcomes of therapy. J Inherit Metab Dis. 2011;34:643-50 pubmed publisher
    ..hypertension (PAH) and hepatopulmonary syndrome (HPS) are rare pulmonary vascular complications of type 1 Gaucher disease (GD1)...
  2. Sun Y, Liou B, Ran H, Skelton M, Williams M, Vorhees C, et al. Neuronopathic Gaucher disease in the mouse: viable combined selective saposin C deficiency and mutant glucocerebrosidase (V394L) mice with glucosylsphingosine and glucosylceramide accumulation and progressive neurological deficits. Hum Mol Genet. 2010;19:1088-97 pubmed publisher
    b>Gaucher disease is caused by defective acid beta-glucosidase (GCase) function. Saposin C is a lysosomal protein needed for optimal GCase activity...
  3. Zimran A, Altarescu G, Elstein D. Nonprecipitous changes upon withdrawal from imiglucerase for Gaucher disease because of a shortage in supply. Blood Cells Mol Dis. 2011;46:111-4 pubmed publisher
    Because of an unpredicted and unavoidable shortage in global supplies of imiglucerase for Gaucher disease, we collected clinical and laboratory data from patients who were evaluated ? 6months before drug withdrawal and then retested ..
  4. Giraldo P, Alfonso P, Atutxa K, Fernández Galán M, Barez A, Franco R, et al. Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project. Haematologica. 2009;94:1771-5 pubmed publisher
    ..clinical experience with miglustat (Zavesca), an oral inhibitor of glucosylceramide synthase, in type 1 Gaucher disease. We report data from a prospective, open-label investigational study that evaluated substrate reduction ..
  5. Lu J, Yang C, Chen M, Ye D, Lonser R, Brady R, et al. Histone deacetylase inhibitors prevent the degradation and restore the activity of glucocerebrosidase in Gaucher disease. Proc Natl Acad Sci U S A. 2011;108:21200-5 pubmed publisher
    b>Gaucher disease (GD) is caused by a spectrum of genetic mutations within the gene encoding the lysosomal enzyme glucocerebrosidase (GCase)...
  6. Zver S, Bracko M, Andoljsek D. Primary bone angiosarcoma in a patient with Gaucher disease. Int J Hematol. 2010;92:374-7 pubmed publisher
    Skeletal pain and the resulting skeletal complications are common in Gaucher disease. The patients therefore usually receive symptomatic treatment and only rarely undergo additional diagnostic procedures...
  7. Stein P, Malhotra A, Haims A, Pastores G, Mistry P. Focal splenic lesions in type I Gaucher disease are associated with poor platelet and splenic response to macrophage-targeted enzyme replacement therapy. J Inherit Metab Dis. 2010;33:769-74 pubmed publisher
    Focal splenic lesions (FSL) occur in Gaucher disease type I (GD1), but their clinical significance is not known...
  8. Cherin P, Rose C, de Roux Serratrice C, Tardy D, Dobbelaere D, Grosbois B, et al. The neurological manifestations of Gaucher disease type 1: the French Observatoire on Gaucher disease (FROG). J Inherit Metab Dis. 2010;33:331-8 pubmed publisher
    b>Gaucher disease (GD), the most prevalent inherited lysosomal storage disorder, is caused by deficient glucocerebrosidase activity. Type 1 GD (GD1), the most common variant, is classically considered non-neuronopathic...
  9. Zimran A, Altarescu G, Elstein D. Pilot study using ambroxol as a pharmacological chaperone in type 1 Gaucher disease. Blood Cells Mol Dis. 2013;50:134-7 pubmed publisher
    ..the tolerability and efficacy of ambroxol as a pharmacological chaperone in patients with symptomatic, type 1 Gaucher disease who present with measurable disease parameters but are not receiving enzyme replacement therapy (ERT) in ..
  10. Taddei T, Dziura J, Chen S, Yang R, Hyogo H, Sullards C, et al. High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease. J Inherit Metab Dis. 2010;33:291-300 pubmed publisher
    In Gaucher disease (GD), lysosomal glucocerebrosidase deficiency results in glucosylceramide accumulation in macrophage lysosomes. Hepatocytes do not accumulate glucosylceramide due in part to biliary secretion...
  11. Franco M, Collec E, Connes P, van den Akker E, Billette De Villemeur T, Belmatoug N, et al. Abnormal properties of red blood cells suggest a role in the pathophysiology of Gaucher disease. Blood. 2013;121:546-55 pubmed publisher
    b>Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase deficiency...
  12. Marshall J, McEachern K, Chuang W, Hutto E, Siegel C, Shayman J, et al. Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy. J Inherit Metab Dis. 2010;33:281-9 pubmed publisher
    b>Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (acid beta-glucosidase), with consequent cellular accumulation of glucosylceramide (GL-1)...
  13. Vaccaro A, Motta M, Tatti M, Scarpa S, Masuelli L, Bhat M, et al. Saposin C mutations in Gaucher disease patients resulting in lysosomal lipid accumulation, saposin C deficiency, but normal prosaposin processing and sorting. Hum Mol Genet. 2010;19:2987-97 pubmed publisher
    b>Gaucher disease (GD) is characterized by accumulation of glucosylceramide (GC) in the cells of monocyte/macrophage system...
  14. Aerts J, Kallemeijn W, Wegdam W, Joao Ferraz M, van Breemen M, Dekker N, et al. Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies. J Inherit Metab Dis. 2011;34:605-19 pubmed publisher
    ..These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease...
  15. Dehay B, Martinez Vicente M, Caldwell G, Caldwell K, Yue Z, Cookson M, et al. Lysosomal impairment in Parkinson's disease. Mov Disord. 2013;28:725-32 pubmed publisher
  16. Wennekes T, van den Berg R, Boot R, van der Marel G, Overkleeft H, Aerts J. Glycosphingolipids--nature, function, and pharmacological modulation. Angew Chem Int Ed Engl. 2009;48:8848-69 pubmed publisher
    ..Special attention is paid to the clinical relevance of compounds directed at interfering with the factors responsible for glycosphingolipid metabolism. ..
  17. Elstein D, Cohn G, Wang N, Djordjevic M, Brutaru C, Zimran A. Early achievement and maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease. Blood Cells Mol Dis. 2011;46:119-23 pubmed publisher
    ..described to monitor achievement, maintenance and continuity of therapeutic response in patients with type 1 Gaucher disease receiving enzyme replacement therapy...
  18. Mistry P, Deegan P, Vellodi A, Cole J, Yeh M, Weinreb N. Timing of initiation of enzyme replacement therapy after diagnosis of type 1 Gaucher disease: effect on incidence of avascular necrosis. Br J Haematol. 2009;147:561-70 pubmed publisher
    ..enzyme replacement therapy with imiglucerase (ERT) and incidence of avascular necrosis (AVN) in type 1 Gaucher disease (GD1), and to determine whether the time interval between diagnosis and initiation of ERT influences the ..
  19. Patnaik S, Zheng W, Choi J, Motabar O, Southall N, Westbroek W, et al. Discovery, structure-activity relationship, and biological evaluation of noninhibitory small molecule chaperones of glucocerebrosidase. J Med Chem. 2012;55:5734-48 pubmed publisher
    A major challenge in the field of Gaucher disease has been the development of new therapeutic strategies including molecular chaperones...
  20. Mistry P, Weinreb N, Kaplan P, Cole J, Gwosdow A, HANGARTNER T. Osteopenia in Gaucher disease develops early in life: response to imiglucerase enzyme therapy in children, adolescents and adults. Blood Cells Mol Dis. 2011;46:66-72 pubmed publisher
    In Gaucher disease (GD), acid-?-glucosidase (GBA1) gene mutations result in defective glucocerebrosidase and variable combinations of hematological, visceral, and diverse bone disease...
  21. Goldin E, Zheng W, Motabar O, Southall N, Choi J, Marugan J, et al. High throughput screening for small molecule therapy for Gaucher disease using patient tissue as the source of mutant glucocerebrosidase. PLoS ONE. 2012;7:e29861 pubmed publisher
    b>Gaucher disease (GD), the most common lysosomal storage disorder, results from the inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCase)...
  22. Berger J, Lecourt S, Vanneaux V, Rapatel C, Boisgard S, Caillaud C, et al. Glucocerebrosidase deficiency dramatically impairs human bone marrow haematopoiesis in an in vitro model of Gaucher disease. Br J Haematol. 2010;150:93-101 pubmed publisher
    One of the cardinal symptoms of type 1 Gaucher Disease (GD) is cytopenia, usually explained by bone marrow (BM) infiltration by Gaucher cells and hypersplenism...
  23. Benito J, Garcia Fernandez J, Ortiz Mellet C. Pharmacological chaperone therapy for Gaucher disease: a patent review. Expert Opin Ther Pat. 2011;21:885-903 pubmed publisher
    Mutations in the gene encoding for acid ?-glucosidase (?-glucocerebrosidase, GlcCerase) are seen in Gaucher disease (GD), which give rise to significant protein misfolding effects and result in progressive accumulation of glucosyl ..
  24. Babajani G, Tropak M, Mahuran D, Kermode A. Pharmacological chaperones facilitate the post-ER transport of recombinant N370S mutant ?-glucocerebrosidase in plant cells: evidence that N370S is a folding mutant. Mol Genet Metab. 2012;106:323-9 pubmed publisher
    b>Gaucher disease is a prevalent lysosomal storage disease in which affected individuals inherit mutations in the gene (GBA1) encoding lysosomal acid ?-glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45)...
  25. Trapero A, Gonzalez Bulnes P, Butters T, Llebaria A. Potent aminocyclitol glucocerebrosidase inhibitors are subnanomolar pharmacological chaperones for treating gaucher disease. J Med Chem. 2012;55:4479-88 pubmed publisher
    ..have been found to be potent inhibitors of glucocerebrosidase (GCase), the ?-glucosidase enzyme deficient in Gaucher disease (GD)...
  26. Maor G, Filocamo M, Horowitz M. ITCH regulates degradation of mutant glucocerebrosidase: implications to Gaucher disease. Hum Mol Genet. 2013;22:1316-27 pubmed publisher
    ..important in cases of diseases in which the mutant proteins undergo ER-associated degradation (ERAD), as in Gaucher disease (GD)...
  27. Farfel Becker T, Vitner E, Pressey S, Eilam R, Cooper J, Futerman A. Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease. Hum Mol Genet. 2011;20:1375-86 pubmed publisher
    b>Gaucher disease (GD), the most common lysosomal storage disorder, is caused by a deficiency in the lysosomal enzyme glucocerebrosidase (GlcCerase), which results in intracellular accumulation of glucosylceramide (GlcCer)...
  28. Giraldo P, Irún P, Alfonso P, Dalmau J, Fernández Galán M, Figueredo A, et al. Evaluation of Spanish Gaucher disease patients after a 6-month imiglucerase shortage. Blood Cells Mol Dis. 2011;46:115-8 pubmed publisher
    ..A position statement from the European Working Group for Gaucher Disease and European Gaucher Alliance established a set of key recommendations for identifying and monitoring at-risk ..
  29. Farfel Becker T, Vitner E, Futerman A. Animal models for Gaucher disease research. Dis Model Mech. 2011;4:746-52 pubmed publisher
    b>Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene...
  30. Castilla J, Rísquez R, Cruz D, Higaki K, Nanba E, Ohno K, et al. Conformationally-locked N-glycosides with selective ?-glucosidase inhibitory activity: identification of a new non-iminosugar-type pharmacological chaperone for Gaucher disease. J Med Chem. 2012;55:6857-65 pubmed publisher
    ..further assayed as inhibitor of the human lysosomal ?-glucocerebrosidase and as pharmacological chaperone in Gaucher disease fibroblasts...
  31. McNeill A, Duran R, Proukakis C, Bras J, Hughes D, Mehta A, et al. Hyposmia and cognitive impairment in Gaucher disease patients and carriers. Mov Disord. 2012;27:526-32 pubmed publisher
    The objective of this study was to assess a cohort of Gaucher disease patients and their heterozygous carrier relatives for potential clinical signs of early neurodegeneration...
  32. Zhang C, Stein P, Liu J, Wang Z, Yang R, Cho J, et al. Genome-wide association study of N370S homozygous Gaucher disease reveals the candidacy of CLN8 gene as a genetic modifier contributing to extreme phenotypic variation. Am J Hematol. 2012;87:377-83 pubmed publisher
    Mutations in GBA1 gene result in defective acid ?-glucosidase and the complex phenotype of Gaucher disease (GD) related to the accumulation of glucosylceramide-laden macrophages...
  33. Dekker N, van Dussen L, Hollak C, Overkleeft H, Scheij S, Ghauharali K, et al. Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response. Blood. 2011;118:e118-27 pubmed publisher
    b>Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, leads to prominent glucosylceramide accumulation in lysosomes of tissue macrophages (Gaucher cells)...
  34. Luan Z, Higaki K, Aguilar Moncayo M, Li L, Ninomiya H, Nanba E, et al. A Fluorescent sp2-iminosugar with pharmacological chaperone activity for gaucher disease: synthesis and intracellular distribution studies. Chembiochem. 2010;11:2453-64 pubmed publisher
    b>Gaucher disease (GD) is the most prevalent lysosomal-storage disorder, it is caused by mutations of acid ?-glucosidase (?-glucocerebrosidase; ?-Glu)...
  35. Karageorgos L, Lancaster M, Nimmo J, Hopwood J. Gaucher disease in sheep. J Inherit Metab Dis. 2011;34:209-15 pubmed publisher
    b>Gaucher disease, an autosomal recessive lysosomal storage disorder caused by mutations in the ?-glucocerebrosidase gene, was recently discovered in sheep on a "Southdown" sheep stud in Victoria, Australia...
  36. Lukina E, Watman N, Arreguin E, Banikazemi M, Dragosky M, Iastrebner M, et al. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood. 2010;116:893-9 pubmed publisher
    ..inhibitor of glucosylceramide synthase, is under development as an oral substrate reduction therapy for Gaucher disease type 1 (GD1)...
  37. Hollak C, de Fost M, van Dussen L, vom Dahl S, Aerts J. Enzyme therapy for the treatment of type 1 Gaucher disease: clinical outcomes and dose - response relationships. Expert Opin Pharmacother. 2009;10:2641-52 pubmed publisher
    Enzyme therapy for Gaucher disease has improved the lives of many patients, by reducing the burden of their disease...
  38. Sun Y, Ran H, Zamzow M, Kitatani K, Skelton M, Williams M, et al. Specific saposin C deficiency: CNS impairment and acid beta-glucosidase effects in the mouse. Hum Mol Genet. 2010;19:634-47 pubmed publisher
    ..The few patients with saposin C deficiency develop a Gaucher disease-like central nervous system (CNS) phenotype attributed to diminished glucosylceramide (GC) cleavage activity ..
  39. Al Owain M, Al Zaidan H, Al Hashem A, Kattan H, Al Dowaish A. Munchausen syndrome by proxy mimicking as Gaucher disease. Eur J Pediatr. 2010;169:1029-32 pubmed publisher
    ..beta-Glucosylceramidase enzyme activity on dried blood spot was suggestive of Gaucher disease. However, the enzyme level on cultured skin fibroblast was not consistent with Gaucher disease...
  40. Trapero A, Llebaria A. Glucocerebrosidase inhibitors for the treatment of Gaucher disease. Future Med Chem. 2013;5:573-90 pubmed publisher
    b>Gaucher disease is a progressive lysosomal storage disorder caused by a deficiency in the activity of ?-glucocerebrosidase and is characterized by the accumulation of the glycosphingolipid glucosylceramide in the lysosomes of macrophages ..
  41. Bultron G, Kacena K, Pearson D, Boxer M, Yang R, Sathe S, et al. The risk of Parkinson's disease in type 1 Gaucher disease. J Inherit Metab Dis. 2010;33:167-73 pubmed publisher
    In Gaucher disease, defective lysosomal glucocerebrosidase due to mutations in the GBA1 gene results in lysosomal accumulation of glucocerebroside in mononuclear phagocytes and a multisystemic phenotype...
  42. Xu Y, Jia L, Quinn B, Zamzow M, Stringer K, Aronow B, et al. Global gene expression profile progression in Gaucher disease mouse models. BMC Genomics. 2011;12:20 pubmed publisher
    b>Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide...
  43. Gupta N, Oppenheim I, Kauvar E, Tayebi N, Sidransky E. Type 2 Gaucher disease: phenotypic variation and genotypic heterogeneity. Blood Cells Mol Dis. 2011;46:75-84 pubmed publisher
    b>Gaucher disease (GD), the most common lysosomal storage disease, results from a deficiency of the lysosomal enzyme glucocerebrosidase...
  44. Goker Alpan O, Stubblefield B, Giasson B, Sidransky E. Glucocerebrosidase is present in α-synuclein inclusions in Lewy body disorders. Acta Neuropathol. 2010;120:641-9 pubmed publisher
    Mutations in the gene encoding the lysosomal enzyme glucocerebrosidase, known to cause Gaucher disease (GD), are a risk factor for the development of Parkinson disease (PD) and related disorders...
  45. Weinreb N, Goldblatt J, Villalobos J, Charrow J, Cole J, Kerstenetzky M, et al. Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment. J Inherit Metab Dis. 2013;36:543-53 pubmed publisher
    We studied the effect of long-term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1).
  46. Ong D, Wang Y, Tan Y, Yates J, Mu T, Kelly J. FKBP10 depletion enhances glucocerebrosidase proteostasis in Gaucher disease fibroblasts. Chem Biol. 2013;20:403-15 pubmed publisher
    ..Thus, targeting FKBP10 appears to be a heretofore unrecognized therapeutic strategy to ameliorate LSDs...
  47. Zimran A. How I treat Gaucher disease. Blood. 2011;118:1463-71 pubmed publisher
    This review presents a cohesive approach to treating patients with Gaucher disease. The spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one disease-specific treatment...
  48. Hollak C, Belmatoug N, Cole J, vom Dahl S, Deegan P, Goldblatt J, et al. Characteristics of type I Gaucher disease associated with persistent thrombocytopenia after treatment with imiglucerase for 4-5 years. Br J Haematol. 2012;158:528-38 pubmed publisher
    The characteristics of Gaucher disease (GD) associated with persistent thrombocytopenia despite imiglucerase enzyme therapy in type 1 GD (GD1) were investigated by retrospective analysis of International Collaborative Gaucher Group (ICGG)..
  49. Goker Alpan O. Therapeutic approaches to bone pathology in Gaucher disease: past, present and future. Mol Genet Metab. 2011;104:438-47 pubmed publisher
    Enzyme replacement therapy (ERT) is effective for the treatment of the systemic manifestations of Gaucher disease (GD) and can have a significant impact on skeletal manifestations...
  50. Aviner S, Garty B, Rachmel A, Baris H, Sidransky E, Shuffer A, et al. Type 2 Gaucher disease occurs in Ashkenazi Jews but is surprisingly rare. Blood Cells Mol Dis. 2009;43:294-7 pubmed publisher
    Patients with Gaucher disease (GD) are divided into three types based on the presence and rate of progression of the neurologic manifestations...
  51. Ben Turkia H, Riahi I, Azzouz H, Ladab S, Cherif W, Ben Chehida A, et al. [Phenotype and mutational spectrum in Tunisian pediatric gaucher disease]. Tunis Med. 2010;88:158-62 pubmed
    b>Gaucher disease (GD) is a sphingolipidosis with heterogeneous phenotypic expression...
  52. Wang G, Twigg G, Butters T, Zhang S, Zhang L, Zhang L, et al. Synthesis of N-substituted ?-hexonolactams as pharmacological chaperones for the treatment of N370S mutant Gaucher disease. Org Biomol Chem. 2012;10:2923-7 pubmed publisher
    ..The structure-activity relationships are also discussed. These novel N-alkylated iminosugars are promising pharmacological chaperones for the treatment of N370S mutant Gaucher disease.
  53. Lu J, Chiang J, Iyer R, Thompson E, Kaneski C, Xu D, et al. Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl. Proc Natl Acad Sci U S A. 2010;107:21665-70 pubmed publisher
    b>Gaucher disease (GD), the most common lysosomal storage disorder of humans, is caused by mutations in the gene coding for the enzyme glucocerebrosidase (GCase)...
  54. Alfonso P, Pampín S, García Rodríguez B, Tejedor T, Dominguez C, Rodriguez Rey J, et al. Characterization of the c.(-203)A>G variant in the glucocerebrosidase gene and its association with phenotype in Gaucher disease. Clin Chim Acta. 2011;412:365-9 pubmed publisher
    b>Gaucher disease (GD) is a rare autosomal recessive disorder caused mainly by mutations in the glucocerebrosidase (GBA) gene...
  55. Witte M, Kallemeijn W, Aten J, Li K, Strijland A, Donker Koopman W, et al. Ultrasensitive in situ visualization of active glucocerebrosidase molecules. Nat Chem Biol. 2010;6:907-13 pubmed publisher
    Deficiency of glucocerebrosidase (GBA) underlies Gaucher disease, a common lysosomal storage disorder. Carriership for Gaucher disease has recently been identified as major risk for parkinsonism...
  56. Pastores G. Recombinant glucocerebrosidase (imiglucerase) as a therapy for Gaucher disease. BioDrugs. 2010;24:41-7 pubmed publisher
    Imiglucerase is a recombinant formulation of human glucocerebrosidase, which is administered to patients with Gaucher disease (GD) as enzyme replacement therapy (ERT)...
  57. Osellame L, Rahim A, Hargreaves I, Gegg M, Richard Londt A, Brandner S, et al. Mitochondria and quality control defects in a mouse model of Gaucher disease--links to Parkinson's disease. Cell Metab. 2013;17:941-53 pubmed publisher
    Mutations in the glucocerebrosidase (gba) gene cause Gaucher disease (GD), the most common lysosomal storage disorder, and increase susceptibility to Parkinson's disease (PD)...
  58. Mekinian A, Stirnemann J, Belmatoug N, Heraoui D, Fantin B, Fain O, et al. Ferritinemia during type 1 Gaucher disease: mechanisms and progression under treatment. Blood Cells Mol Dis. 2012;49:53-7 pubmed publisher
    Earlier results highlighted hyperferritinemia during type-1 Gaucher disease (GD), but its potential mechanisms and long-term progression remained unexamined.
  59. Mucci J, Scian R, De Francesco P, García F, Ceci R, Fossati C, et al. Induction of osteoclastogenesis in an in vitro model of Gaucher disease is mediated by T cells via TNF-?. Gene. 2012;509:51-9 pubmed publisher
    b>Gaucher disease is a lysosomal storage disorder caused by deficiency of glucocerebrosidase enzymatic activity leading to accumulation of its substrate glucocerebrosidase mainly in macrophages...
  60. Cabrera Salazar M, Bercury S, Ziegler R, Marshall J, Hodges B, Chuang W, et al. Intracerebroventricular delivery of glucocerebrosidase reduces substrates and increases lifespan in a mouse model of neuronopathic Gaucher disease. Exp Neurol. 2010;225:436-44 pubmed publisher
    b>Gaucher disease is caused by a deficit in the enzyme glucocerebrosidase...
  61. Lukina E, Watman N, Arreguin E, Dragosky M, Iastrebner M, Rosenbaum H, et al. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood. 2010;116:4095-8 pubmed publisher
    Eliglustat tartrate is an investigational oral substrate reduction therapy for Gaucher disease type 1 that is pharmacologically distinct from intravenous enzyme replacement therapy...
  62. Jeong S, Park S, Kim H. Clinical and genetic characteristics of Korean patients with Gaucher disease. Blood Cells Mol Dis. 2011;46:11-4 pubmed publisher
    b>Gaucher disease (GD) is an autosomal recessive glycolipid lysosomal storage disease caused by a deficiency of the ?-glucocerebrosidase enzyme (GBA). Allelic heterogeneity in GD has been well described...
  63. Hein L, Duplock S, Fuller M. Selective reduction of bis(monoacylglycero)phosphate ameliorates the storage burden in a THP-1 macrophage model of Gaucher disease. J Lipid Res. 2013;54:1691-7 pubmed publisher
    ..Impaired lysosomal degradation of the sphingolipid glucosylceramide (GC) occurs in Gaucher disease due to an inherited deficiency of acid ?-glucosidase, with secondary BMP alterations...
  64. Mistry P, Liu J, Yang M, Nottoli T, McGrath J, Jain D, et al. Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage. Proc Natl Acad Sci U S A. 2010;107:19473-8 pubmed publisher
    In nonneuronopathic type 1 Gaucher disease (GD1), mutations in the glucocerebrosidase gene (GBA1) gene result in glucocerebrosidase deficiency and the accumulation of its substrate, glucocerebroside (GL-1), in the lysosomes of ..
  65. Sun Y, Liou B, Quinn B, Ran H, Xu Y, Grabowski G. In vivo and ex vivo evaluation of L-type calcium channel blockers on acid beta-glucosidase in Gaucher disease mouse models. PLoS ONE. 2009;4:e7320 pubmed publisher
    b>Gaucher disease is a lysosomal storage disease caused by mutations in acid beta-glucosidase (GCase) leading to defective hydrolysis and accumulation of its substrates...
  66. van Dussen L, Zimran A, Akkerman E, Aerts J, Petakov M, Elstein D, et al. Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease. Blood Cells Mol Dis. 2013;50:206-11 pubmed publisher
    ..recombinant human beta-glucocerebrosidase recently approved in the United States for the treatment of type 1 Gaucher disease (GD)...
  67. Bussink A, Verhoek M, Vreede J, Ghauharali van der Vlugt K, Donker Koopman W, Sprenger R, et al. Common G102S polymorphism in chitotriosidase differentially affects activity towards 4-methylumbelliferyl substrates. FEBS J. 2009;276:5678-88 pubmed publisher
    ..Plasma chitotriosidase activity reflects the presence of lipid-laden macrophages in patients with Gaucher disease. CHIT1 activity can be conveniently measured using fluorogenic 4-methylumbelliferyl (4MU)-chitotrioside or ..
  68. Sanders A, Hemmelgarn H, Melrose H, Hein L, Fuller M, Clarke L. Transgenic mice expressing human glucocerebrosidase variants: utility for the study of Gaucher disease. Blood Cells Mol Dis. 2013;51:109-15 pubmed publisher
    b>Gaucher disease is an autosomal recessively inherited storage disorder caused by deficiency of the lysosomal hydrolase, acid ?-glucosidase...
  69. Vitner E, Platt F, Futerman A. Common and uncommon pathogenic cascades in lysosomal storage diseases. J Biol Chem. 2010;285:20423-7 pubmed publisher
    ..We now review how these cascades impact upon LSD pathology and suggest how intervention in the pathways may lead to novel therapeutic approaches...
  70. Zimran A, Brill Almon E, Chertkoff R, Petakov M, Blanco Favela F, Muñoz E, et al. Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood. 2011;118:5767-73 pubmed publisher
    ..Biotherapeutics, Carmiel, Israel) is a novel plant cell-derived recombinant human ?-glucocerebrosidase for Gaucher disease. A phase 3, double-blind, randomized, parallel-group, comparison-dose (30 vs 60 U/kg body weight/infusion) ..
  71. Lee Y, Kim S, Heo T. Protective effect of catechin in type I Gaucher disease cells by reducing endoplasmic reticulum stress. Biochem Biophys Res Commun. 2011;413:254-8 pubmed publisher
    b>Gaucher disease (GD) is the most common lysosomal storage disorder (LSD) and is divided into three phenotypes, I, II, and III. Type I is the most prevalent form and has its onset in adulthood...
  72. Vitner E, Dekel H, Zigdon H, Shachar T, Farfel Becker T, Eilam R, et al. Altered expression and distribution of cathepsins in neuronopathic forms of Gaucher disease and in other sphingolipidoses. Hum Mol Genet. 2010;19:3583-90 pubmed publisher
    The neuronopathic forms of the human inherited metabolic disorder, Gaucher disease (GD), are characterized by severe neuronal loss, astrogliosis and microglial proliferation, but the cellular and molecular pathways causing these changes ..
  73. Sardi S, Clarke J, Viel C, Chan M, Tamsett T, Treleaven C, et al. Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies. Proc Natl Acad Sci U S A. 2013;110:3537-42 pubmed publisher
    ..Hence, increasing glucocerebrosidase activity in the CNS represents a potential therapeutic strategy for GBA1-related and non-GBA1-associated synucleinopathies, including PD...
  74. Mistry P, Taddei T, vom Dahl S, Rosenbloom B. Gaucher disease and malignancy: a model for cancer pathogenesis in an inborn error of metabolism. Crit Rev Oncog. 2013;18:235-46 pubmed
    Clinical observations spanning almost half a century have demonstrated a consistent association of type 1 Gaucher disease (GD1) and cancers. However, the cellular and molecular bases of the association are not understood...
  75. Mucci J, Suqueli García F, De Francesco P, Ceci R, di Genaro S, Fossati C, et al. Uncoupling of osteoblast-osteoclast regulation in a chemical murine model of Gaucher disease. Gene. 2013;532:186-91 pubmed publisher
    b>Gaucher disease (GD) is caused by mutations in the GBA gene that confer a deficient level of activity of glucocerebrosidase (GCase)...
  76. Gegg M, Burke D, Heales S, Cooper J, Hardy J, Wood N, et al. Glucocerebrosidase deficiency in substantia nigra of parkinson disease brains. Ann Neurol. 2012;72:455-63 pubmed publisher
    ..Biochemical changes involved in PD pathogenesis affect wild-type GCase protein expression in vitro, and these could be contributing factors to the GCase deficiency observed in sporadic PD brains. ..
  77. Jovic M, Kean M, Szentpetery Z, Polevoy G, Gingras A, Brill J, et al. Two phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, ?-glucocerebrosidase. Mol Biol Cell. 2012;23:1533-45 pubmed publisher
    b>Gaucher disease is a lysosomal storage disorder caused by a defect in the degradation of glucosylceramide catalyzed by the lysosomal enzyme ?-glucocerebrosidase (GBA)...
  78. Machaczka M, Hast R, Dahlman I, Lerner R, Klimkowska M, Engvall M, et al. Substrate reduction therapy with miglustat for type 1 Gaucher disease: a retrospective analysis from a single institution. Ups J Med Sci. 2012;117:28-34 pubmed publisher
    b>Gaucher disease (GD) is an infrequent progressive multisystem lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme, glucocerebrosidase...
  79. Bodamer O, Hung C. Laboratory and genetic evaluation of Gaucher disease. Wien Med Wochenschr. 2010;160:600-4 pubmed publisher
    b>Gaucher disease (GD) is an inherited lysosomal storage disorder due to deficiency of glucocerebrosidase...
  80. Saunders Pullman R, Hagenah J, Dhawan V, Stanley K, Pastores G, Sathe S, et al. Gaucher disease ascertained through a Parkinson's center: imaging and clinical characterization. Mov Disord. 2010;25:1364-72 pubmed publisher
    Among the genes implicated for parkinsonism is glucocerebrosidase (GBA), which causes Gaucher disease (GD)...
  81. Khanna R, Benjamin E, Pellegrino L, Schilling A, Rigat B, Soska R, et al. The pharmacological chaperone isofagomine increases the activity of the Gaucher disease L444P mutant form of beta-glucosidase. FEBS J. 2010;277:1618-38 pubmed publisher
    b>Gaucher disease is caused by mutations in the gene that encodes the lysosomal enzyme acid beta-glucosidase (GCase)...
  82. Cindik N, Ozcay F, Suren D, Akkoyun I, Gokdemir M, Varan B, et al. Gaucher disease with communicating hydrocephalus and cardiac involvement. Clin Cardiol. 2010;33:E26-30 pubmed publisher
    A 14-year-old female with Gaucher disease presented with hydrocephalus, corneal opacities, cirrhosis, and cardiac valvular involvement. A homozygous D409H mutation was identified...
  83. Sardi S, Singh P, Cheng S, Shihabuddin L, Schlossmacher M. Mutant GBA1 expression and synucleinopathy risk: first insights from cellular and mouse models. Neurodegener Dis. 2012;10:195-202 pubmed publisher
    ..Homozygous GBA1 mutations lead to reduced GBA1 lysosomal activity underlying three variants of Gaucher disease (GD)...
  84. Sardi S, Clarke J, Kinnecom C, Tamsett T, Li L, Stanek L, et al. CNS expression of glucocerebrosidase corrects alpha-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy. Proc Natl Acad Sci U S A. 2011;108:12101-6 pubmed publisher
    Emerging genetic and clinical evidence suggests a link between Gaucher disease and the synucleinopathies Parkinson disease and dementia with Lewy bodies...
  85. Elstein D, Foldes A, Zahrieh D, Cohn G, Djordjevic M, Brutaru C, et al. Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction. Blood Cells Mol Dis. 2011;47:56-61 pubmed publisher
    Since bone pathology is a major concern in type 1 Gaucher disease (GD1), we evaluated bone mineral density (BMD) in adults receiving velaglucerase alfa in the seminal Phase I/II and extension trial...
  86. Deegan P, Pavlova E, Tindall J, Stein P, Bearcroft P, Mehta A, et al. Osseous manifestations of adult Gaucher disease in the era of enzyme replacement therapy. Medicine (Baltimore). 2011;90:52-60 pubmed publisher
    Enzyme replacement therapy (ERT) for Gaucher disease with mannose-terminated glucocerebrosidase has proved its therapeutic position with salutary effects on hematologic abnormalities, visceral infiltration, and quality of life...
  87. Machaczka M, Klimkowska M, Regenthal S, Hagglund H. Gaucher disease with foamy transformed macrophages and erythrophagocytic activity. J Inherit Metab Dis. 2011;34:233-5 pubmed publisher
    ..Here, we describe the case of an adult non-Jewish Caucasian male with a heterozygous Gaucher disease type 1 (mutations c.1226A>G and c...
  88. Biegstraaten M, Mengel E, Marodi L, Petakov M, Niederau C, Giraldo P, et al. Peripheral neuropathy in adult type 1 Gaucher disease: a 2-year prospective observational study. Brain. 2010;133:2909-19 pubmed publisher
    Type 1 Gaucher disease is currently categorized as non-neuronopathic, although recent studies suggest peripheral neurological manifestations...
  89. Mignot C, Gelot A, de Villemeur T. Gaucher disease. Handb Clin Neurol. 2013;113:1709-15 pubmed publisher
    b>Gaucher disease is an autosomal recessive condition due to glucocerebrosidase deficiency responsible for the lysosomal accumulation of glucosylceramide, a complex lipid derived from cell membranes, mainly in macrophages...
  90. Hollak C, vom Dahl S, Aerts J, Belmatoug N, Bembi B, Cohen Y, et al. Force majeure: therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease. Blood Cells Mol Dis. 2010;44:41-7 pubmed publisher
    b>Gaucher disease is the first lysosomal disorder for which clinically effective enzyme replacement therapy has been introduced...