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 supranuklear 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

Gaucher Disease GM1-Gangliosidosis GM2-Gangliosidosis
Retrieve
Natural history study for pediatric parents with early onset of either GM1 gangliosidoses, GM 2 gangliosidoses, or Gaucher disease typ 2
Age

Birthdate after or at 1 of january 2000

Status active

Patient admission recruiting

Institution SphinCS GmbH

Natural-History-Study
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

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

Enzyme Replacement Therapy: A New Treatment Concept in Gaucher Disease

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

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

Bone Complications in Children with Gaucher Disease

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

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

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

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

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

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

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

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

The Management of Pregnancy in Gaucher Disease

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

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

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

Morbus Gaucher: Eine Stoffwechselstörung Mit Typischer, Kutaner Manifestation

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

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

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

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

Rheumatologic Aspects of Lysosomal Storage Diseases

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?

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

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

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

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

Morbus Gaucher, Mukopolysaccharidose Typ I (Scheie) Und Morbus Fabry

Michels, H. and E. Mengel.

Lysosomal Storage Diseases as Differential Diagnoses to Rheumatic Disorders

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

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

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

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

Lysosomal Acid Lipase Deficiency: Expanding Differential Diagnosis

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

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

Vom Dahl, S. and E. Mengel.

Lysosomal Storage Diseases as Differential Diagnosis of Hepatosplenomegaly

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

Gaucher Disease and Miscellaneous

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

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)

At present we have no literature available.