Lysomal Storage Disorder

The Hyena

Gaucher Disease

Gaucher Disease is an autosomal recessively inherited lysosomal storage disorder caused by the deficiency of the lysosomal enzyme beta-glucocerebrosidase. This leads to intracellular storage of glycosylceramide in the cells of various organs, especially in the liver, spleen and bone marrow. Three phenotypes are distinguished: Gaucher disease type I, type II and type III. Gaucher disease type I, the most common phenotype, describes the chronic non-neurological form and is characterized by hepatosplenomegaly, bone symptoms (pain, bone infarction osteonecrosis), thrombocytopenia and anemia. Gaucher disease type II is the rarest form and is distinguished by manifestation in infancy with severe rapidly progressive neurological symptoms (bulbar and pyramidal signs, myoclonic epilepsy). In addition to the clinical signs of Gaucher disease type I, Gaucher disease type III combines progressive neurological symptoms (oculomotor apraxia, ataxia, epilepsy). Therapeutically, 4 approved drugs are available (enzyme replacement therapies with imiglucerase or velaglucerase alfa for Gaucher disease type I and type III, substrate reduction therapies with miglustat or eliglustat for Gaucher disease type I).

Gaucher Disease | SphinCS - Clinical Science for LSD

Etiology: Deficiency of beta-glucocerebrosidase (= beta-glucosidase)
Gene: GBA1 Gene
Mode of inheritance: Autosomal recessive
Phenotypes:

  • Gaucher Disease Type I: chronic non-neuronopathic form
  • Gaucher Disease Type II: acute neuronopathic form
  • Gaucher Disease Type III: chronic neuronopathic form

Leading symptoms:

Gaucher Disease Type I
(Age of onset: childhood, adolescence)

  • Hepatosplenomegaly
  • Bone disease (pain, bone infarction, osteonecrosis)
  • Thrombocytopenia, anemia

Gaucher Disease Type II
(Age of onset: infancy)

  • Hepatosplenomegaly
  • Muscular hypotonia
  • Progressive severe CNS symptoms with bulbar and pyramidal signs, myoclonic epilepsy
  • Congenital ichthyosis

Gaucher Disease Type III
(Age of onset: childhood, adolescence)

  • Hepatosplenomegaly
  • Bone disease (pain, bone infarction, osteonecrosis)
  • Thrombocytopenia, anemia
  • Horizontal supranuclear gaze palsy, initial only slow and hypometric horizontal saccades
  • Myoclonic epilepsy
  • Cognitive impairment

Diagnostics:

  • Measurement of the activity of beta-glucocerebrosidase in leucocytes or dried blood spot
  • Glycosylsphingosin ( LysoGL1 )
  • Molecular genetic analysis of GBA1 Gene

Therapy:

M. Gaucher Typ I

  • Imiglucerase (Cerezyme®)
  • Velaglucerase alfa (VPRIV®)
  • Miglustat
  • Eliglustat (Cerdelga®)

M. Gaucher Typ II

  • Only symptomatic

M. Gaucher Typ III

  • Imiglucerase (Cerezyme®)
  • Velaglucerase alfa (VPRIV®)

Current Studies

The "U.S. National Library of Medicine" provides a complete list of all international studies at www.clinicaltrials.gov. The comparable EU website is less comprehensive: www.clinicaltrialsregister.eu.

Self-help groups

Gaucher Gesellschaft Deutschland e.V.
https://www.ggd-ev.de/

At the moment we are not aware of any self-help groups.

Literature

Baldellou, A., G. Andria, P. E. Campbell, J. Charrow, I. J. Cohen, G. A. Grabowski, C. M. Harris, P. Kaplan, K. McHugh, E. Mengel, and A. Vellodi

Paediatric Non-Neuronopathic Gaucher Disease: Recommendations for Treatment and Monitoring
Eur J Pediatr 163, no. 2 (Feb 2004): 67-75.
Link to the publication

Beck, M., E. Mengel, and R. Barone

Enzyme Replacement Therapy: A New Treatment Concept in Gaucher Disease
Wien Klin Wochenschr 109, no. 3 (Feb 14 1997): 81-5.
Link to the publication

Belmatoug, N., A. Burlina, P. Giraldo, C. J. Hendriksz, D. J. Kuter, E. Mengel, and G. M. Pastores

Gastrointestinal Disturbances and Their Management in Miglustat-Treated Patients
J Inherit Metab Dis (Jul 21 2011).
Link to the publication

Bembi, B., G. Ciana, E. Mengel, M. R. Terk, C. Martini, and R. J. Wenstrup.

Bone Complications in Children with Gaucher Disease
Br J Radiol 75 Suppl 1 (2002): A37-44.
Link to the publication

Biegstraaten, M., T. M. Cox, N. Belmatoug, M. G. Berger, T. Collin-Histed, S. Vom Dahl, M. Di Rocco, C. Fraga, F. Giona, P. Giraldo, M. Hasanhodzic, D. A. Hughes, P. O. Iversen, A. I. Kiewiet, E. Lukina, M. Machaczka, T. Marinakis, E. Mengel, G. M. Pastores, U. Plockinger, H. Rosenbaum, C. Serratrice, A. Symeonidis, J. Szer, J. Timmerman, A. Tylki-Szymanska, M. Weisz Hubshman, D. I. Zafeiriou, A. Zimran, and C. E. M. Hollak.

Management Goals for Type 1 Gaucher Disease: An Expert Consensus Document from the European Working Group on Gaucher Disease
Blood Cells Mol Dis 68 (Feb 2018): 203-08.
Link to the publication

Biegstraaten, M., E. Mengel, L. Marodi, M. Petakov, C. Niederau, P. Giraldo, D. Hughes, M. Mrsic, A. Mehta, C. E. Hollak, and I. N. van Schaik.

Peripheral Neuropathy in Adult Type 1 Gaucher Disease: A 2-Year Prospective Observational Study
Brain 133, no. 10 (Oct 2010): 2909-19.
Link to the publication

Biegstraaten, M., K. A. Wesnes, C. Luzy, M. Petakov, M. Mrsic, C. Niederau, P. Giraldo, D. Hughes, A. Mehta, K. E. Mengel, C. E. Hollak, L. Marodi, and I. N. van Schaik

The Cognitive Profile of Type 1 Gaucher Disease Patients
J Inherit Metab Dis (Feb 21 2012).
Link to the publication

Bremova-Ertl, T., R. Schiffmann, M. C. Patterson, N. Belmatoug, T. Billette de Villemeur, S. Bardins, C. Frenzel, V. Malinova, S. Naumann, J. Arndt, E. Mengel, J. Reinke, R. Strobl, and M. Strupp.

Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings
Front Neurol 8 (2017): 711.
Link to the publication

Davies, E. H., A. Erikson, T. Collin-Histed, E. Mengel, A. Tylki-Szymanska, and A. Vellodi.

Outcome of Type Iii Gaucher Disease on Enzyme Replacement Therapy: Review of 55 Cases
J Inherit Metab Dis 30, no. 6 (Nov 2007): 935-42.
Link to the publication

Davies, E. H., E. Mengel, A. Tylki-Szymanska, G. Kleinotiene, J. Reinke, and A. Vellodi.

Four-Year Follow-up of Chronic Neuronopathic Gaucher Disease in Europeans Using a Modified Severity Scoring Tool
J Inherit Metab Dis (May 28 2011).
Link to the publication

Garbade, S. F., M. Zielonka, K. Mechler, S. Kolker, G. F. Hoffmann, C. Staufner, E. Mengel, and M. Ries.

Fda Orphan Drug Designations for Lysosomal Storage Disorders - a Cross-Sectional Analysis
PLoS One 15, no. 4 (2020): e0230898.
Link to the publication

Granovsky-Grisaru, S., N. Belmatoug, S. vom Dahl, E. Mengel, E. Morris, and A. Zimran

The Management of Pregnancy in Gaucher Disease
Eur J Obstet Gynecol Reprod Biol 156, no. 1 (May 2011): 3-8.
Link to the publication

Hollak, C. E., S. vom Dahl, J. M. Aerts, N. Belmatoug, B. Bembi, Y. Cohen, T. Collin-Histed, P. Deegan, L. van Dussen, P. Giraldo, E. Mengel, H. Michelakakis, J. Manuel, M. Hrebicek, R. Parini, J. Reinke, M. di Rocco, M. Pocovi, M. C. Sa Miranda, A. Tylki-Szymanska, A. Zimran, and T. M. Cox.

Force Majeure: Therapeutic Measures in Response to Restricted Supply of Imiglucerase (Cerezyme) for Patients with Gaucher Disease
Blood Cells Mol Dis 44, no. 1 (Jan 15 2010): 41-7.
Link to the publication

Hopf, S., N. Pfeiffer, M. Liesenfeld, K. E. Mengel, J. B. Hennermann, I. Schmidtmann, and S. Pitz.

A Comprehensive Monocentric Ophthalmic Study with Gaucher Disease Type 3 Patients: Vitreoretinal Lesions, Retinal Atrophy and Characterization of Abnormal Saccades
Orphanet J Rare Dis 14, no. 1 (Nov 14 2019): 257.
Link to the publication

Jansen, T., E. Mengel, M. Beck, and S. Grabbe.

Morbus Gaucher: Eine Stoffwechselstörung Mit Typischer, Kutaner Manifestation
Der Deutsche Dermatologe, no. 3 (2006).

Laudemann, K., L. Moos, E. Mengel, A. Lollert, C. Hoffmann, M. Brixius-Huth, D. Wagner, C. Duber, and G. Staatz.

Evaluation of Treatment Response to Enzyme Replacement Therapy with Velaglucerase Alfa in Patients with Gaucher Disease Using Whole-Body Magnetic Resonance Imaging
Blood Cells Mol Dis 57 (Mar 2016): 35-41.
Link to the publication

Laudemann, K., L. Moos, K. E. Mengel, A. Lollert, J. Reinke, M. Brixius-Huth, D. Wagner, C. Duber, and G. Staatz.

Evaluation of Bone Marrow Infiltration in Non-Neuropathic Gaucher Disease Patients with Use of Whole-Body Mri - a Retrospective Data Analysis
Rofo (Jul 22 2015)
Link to the publication

Lollert, A., K. Laudemann, E. Mengel, C. Hoffmann, L. Moos, J. Reinke, M. Brixius-Huth, J. B. Hennermann, C. Duber, and G. Staatz.

Retrospective Analysis of Whole-Body Magnetic Resonance Imaging of Bone Manifestations in Long-Term Treated Patients with Gaucher Disease Type 1
Klin Padiatr 231, no. 2 (Mar 2019): 52-59.
Link to the publication

Manger, B., E. Mengel, and R. M. Schaefer.

Rheumatologic Aspects of Lysosomal Storage Diseases
Clin Rheumatol 26, no. 3 (Mar 2007): 335-41.
Link to the publication

Manger, B., E. Mengel, R. M. Schaefer, C. Haase, J. Seidel, and H. Michels.

Gaucher Disease, Fabry Disease and Mucopolysaccharidosis Type I - How Can the Rheumatologist Recognise These Patients?
Z Rheumatol (Dec 22 2005).
Link to the publication

Mehta, A., N. Belmatoug, B. Bembi, P. Deegan, D. Elstein, O. Goker-Alpan, E. Lukina, E. Mengel, K. Nakamura, G. M. Pastores, J. P. Lopez, I. Schwartz, C. Serratrice, J. Szer, A. Zimran, M. Di Rocco, Z. Panahloo, D. J. Kuter, and D. Hughes

Exploring the Patient Journey to Diagnosis of Gaucher Disease from the Perspective of 212 Patients with Gaucher Disease and 16 Gaucher Expert Physicians
Mol Genet Metab (Aug 04 2017).
Link to the publication

Mehta, A., D. J. Kuter, S. S. Salek, N. Belmatoug, B. Bembi, J. Bright, S. Vom Dahl, F. Deodato, M. Di Rocco, O. Goker-Alpan, D. A. Hughes, E. A. Lukina, M. Machaczka, E. Mengel, A. Nagral, K. Nakamura, A. Narita, B. Oliveri, G. Pastores, J. Perez-Lopez, U. Ramaswami, I. V. Schwartz, J. Szer, N. J. Weinreb, and A. Zimran.

Presenting Signs and Patient Co-Variables in Gaucher Disease: Outcome of the Gaucher Earlier Diagnosis Consensus (Ged-C) Delphi Initiative
Intern Med J 49, no. 5 (May 2019): 578-91.
Link to the publication

Meikle, P. J., P. D. Whitfield, T. Rozaklis, D. Blacklock, S. Duplock, D. Elstein, A. Zimran, E. Mengel, P. Cannell, J. J. Hopwood, and M. Fuller.

Plasma Lipids Are Altered in Gaucher Disease: Biochemical Markers to Evaluate Therapeutic Intervention
Blood Cells Mol Dis 40, no. 3 (May-Jun 2008): 420-7.
Link to the publication

Michels, H. , E. Mengel, H. I. Huppertz, and R. M. Schaefer.

Morbus Gaucher, Mukopolysaccharidose Typ I (Scheie) Und Morbus Fabry
Monatszeitschrift Kinderheilkunde 154, no. 4 (2006): 297-394.

Michels, H. and E. Mengel.

Lysosomal Storage Diseases as Differential Diagnoses to Rheumatic Disorders
Curr Opin Rheumatol 20, no. 1 (Jan 2008): 76-81.
Link to the publication

Pastores, G. M., M. Petakov, P. Giraldo, H. Rosenbaum, J. Szer, P. B. Deegan, D. J. Amato, E. Mengel, E. S. Tan, R. Chertkoff, E. Brill-Almon, and A. Zimran.

A Phase 3, Multicenter, Open-Label, Switchover Trial to Assess the Safety and Efficacy of Taliglucerase Alfa, a Plant Cell-Expressed Recombinant Human Glucocerebrosidase, in Adult and Pediatric Patients with Gaucher Disease Previously Treated with Imigluc
Blood Cells Mol Dis (Jun 17 2014).
Link to the publication

Ries, M., E. Schaefer, T. Luhrs, L. Mani, J. Kuhn, M. T. Vanier, F. Krummenauer, A. Gal, M. Beck, and E. Mengel.

Critical Assessment of Chitotriosidase Analysis in the Rational Laboratory Diagnosis of Children with Gaucher Disease and Niemann-Pick Disease Type a/B and C
J Inherit Metab Dis 29, no. 5 (Oct 2006): 647-52.
Link to the publication

Schiffmann, R., J. Sevigny, A. Rolfs, E. H. Davies, O. Goker-Alpan, M. Abdelwahab, A. Vellodi, E. Mengel, E. Lukina, H. W. Yoo, T. Collin-Histed, A. Narita, T. Dinur, S. Revel-Vilk, D. Arkadir, J. Szer, M. Wajnrajch, U. Ramaswami, E. Sidransky, A. Donald, and A. Zimran.

The Definition of Neuronopathic Gaucher Disease
J Inherit Metab Dis (Apr 3 2020).
Link to the publication

Valayannopoulos, V., E. Mengel, A. Brassier, and G. Grabowski.

Lysosomal Acid Lipase Deficiency: Expanding Differential Diagnosis
Mol Genet Metab 120, no. 1-2 (Jan - Feb 2017): 62-66.
Link to the publication

Vellodi, A., B. Bembi, T. B. de Villemeur, T. Collin-Histed, A. Erikson, E. Mengel, A. Rolfs, and A. Tylki-Szymanska.

Management of Neuronopathic Gaucher Disease: A European Consensus
J Inherit Metab Dis 24, no. 3 (Jun 2001): 319-27.
Link to the publication

Vellodi, A., A. Tylki-Szymanska, E. H. Davies, E. Kolodny, B. Bembi, T. Collin-Histed, E. Mengel, A. Erikson, and R. Schiffmann.

Management of Neuronopathic Gaucher Disease: Revised Recommendations
J Inherit Metab Dis 32, no. 5 (Oct 2009): 660-4.
Link to the publication

Vom Dahl, S. and E. Mengel.

Lysosomal Storage Diseases as Differential Diagnosis of Hepatosplenomegaly
Best Pract Res Clin Gastroenterol 24, no. 5 (Oct 2010): 619-28.
Link to the publication

Wendt, S., E. Mengel, and M. Beck.

Gaucher Disease and Miscellaneous
Acta Paediatr Suppl 95, no. 451 (Apr 2006): 139-44.
Link to the publication

Yildiz, Y., P. Hoffmann, S. Vom Dahl, B. Breiden, R. Sandhoff, C. Niederau, M. Horwitz, S. Karlsson, M. Filacamo, D. Elstein, M. Beck, K. Sandhoff, E. Mengel, M. C. Gonzalez, M. M. Nothen, E. Sidransky, A. Zimran, and M. Mattheisen.

Functional and Genetic Characterization of the Non-Lysosomal Glucosylceramidase 2 as a Modifier for Gaucher Disease
Orphanet J Rare Dis 8, no. 1 (Sep 26 2013): 151.
Link to the publication

Zimran, A., E. Morris, E. Mengel, P. Kaplan, N. Belmatoug, D. A. Hughes, V. Malinova, R. Heitner, E. Sobreira, M. Mrsic, S. Granovsky-Grisaru, D. Amato, and S. Vom Dahl.

The Female Gaucher Patient: The Impact of Enzyme Replacement Therapy around Key Reproductive Events (Menstruation, Pregnancy and Menopause)
Blood Cells Mol Dis (Jun 5 2009).
Link to the publication

Beck, M., E. R. Valadares, and J. Lotz

Gaucher's Disease: Therapy by Intravenous Infusions of Modified Glucocerebrosidase
Clin Investig 71, no. 1 (Jan 1993): 78. http://dx.doi.org/10.1007/BF00210974.

le Coutre, P., A. Demina, E. Beutler, M. Beck, and P. E. Petrides

Molecular Analysis of Gaucher Disease: Distribution of Eight Mutations and the Complete Gene Deletion in 27 Patients from Germany
Hum Genet 99, no. 6 (Jun 1997): 816-21. http://dx.doi.org/10.1007/s004390050454.

Cox, T. M., J. M. Aerts, G. Andria, M. Beck, N. Belmatoug, B. Bembi, R. Chertkoff, S. Vom Dahl, D. Elstein, A. Erikson, M. Giralt, R. Heitner, C. Hollak, M. Hrebicek, S. Lewis, A. Mehta, G. M. Pastores, A. Rolfs, M. C. Miranda, A. Zimran, and Disease Advisory Council to the European Working Group on Gaucher

The Role of the Iminosugar N-Butyldeoxynojirimycin (Miglustat) in the Management of Type I (Non-Neuronopathic) Gaucher Disease: A Position Statement
J Inherit Metab Dis 26, no. 6 (2003): 513-26.
Link to the publication

At present we have no literature available.

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