Journal of Inherited Metabolic Disease

, Volume 33, Issue 4, pp 339–346 | Cite as

Neuronopathic Gaucher disease: demographic and clinical features of 131 patients enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry

  • Anna Tylki-Szymańska
  • Ashok Vellodi
  • Amal El-Beshlawy
  • J. Alexander Cole
  • Edwin Kolodny
Original Article



To describe demographic, genetic, and clinical characteristics of patients with neuronopathic Gaucher disease (NGD).


All patients enrolled in the Neurological Outcomes Subregistry of the International Collaborative Gaucher Group (ICGG) Gaucher Registry as of June 2007 were identified.


The study cohort comprised 131 patients from 17 countries who were enrolled in the Neurological Outcomes Subregistry. The onset of neurological manifestations had occurred before 2 years of age in 47% (61 out of 131 patients), 2 years of age or older in 41% (54 out of 131), and could not be ascertained in the remaining 12% (16 out of 131). The most common manifestations were inability to look to the extreme up or down (45%, 55 out of 123), abnormally slow object tracking (43%, 53 out of 123), convergent squint (36%, 44 out of 121), and ataxia (15 to 20%, 18–27 out of 117). Seizures were reported in 19 out of 122 patients (16%), and myoclonic seizures were reported in 3 out of 121 patients (2%). The most common genotypes were L444P/L444P (76 out of 108, 70%), L444P/D409H (9 out of 108, 8%), D409H/D409H (8 out of 108, 7%), and L444P/rare allele (6 out of 108, 6%); full sequencing was not performed in all patients.


Neurological manifestations of GD often begin to appear before the age of 2 years. The most common neurological signs and manifestations are brainstem abnormalities and fine motor dysfunction. The most common genotype is L444P/L444P.


Neurological Outcome Gauche Disease Neurological Manifestation Gauche Disease Patient Genzyme Corporation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Gaucher disease


International Collaborative Gaucher Group


neuronopathic Gaucher disease



We would like to thank the patients with neuronopathic Gaucher disease and their physicians and health care personnel who submit data to the Neurological Outcomes Subregistry, the Gaucher Registry support team at Genzyme Corporation, Andrea Gwosdow, Ph.D., for assistance in preparing the manuscript, Robert Brown (Genzyme Corporation) for graphic design of the figure, Michael Yeh, M.D. (Genzyme Corporation), for critical review of the manuscript and Pramod Mistry, M.D., Ph.D., for providing GBA1 gene sequencing for the Egyptian type 3 patients.


  1. Beutler E, Grabowski GA (1995) Gaucher disease. In: Scriver CH, Beaudet AL, Sly WS, Valle D (eds), The metabolic and molecular bases of inherited disease. McGraw Hill, New YorkGoogle Scholar
  2. Charrow J, Andersson HC, Kaplan P, et al (2000) The Gaucher Registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 160:2835–2843CrossRefPubMedGoogle Scholar
  3. Charrow J, Dulisse B, Grabowski GA, Weinreb NJ (2007) The effect of enzyme replacement therapy on bone crisis and bone pain in patients with type 1 Gaucher disease. Clin Genet 71:205–211CrossRefPubMedGoogle Scholar
  4. Choy FYM, Zhang W, Shi H-P et al (2007) Gaucher disease among Chinese patients: review on genotype/phenotype correlation from 29 patients and identification of novel and rare alleles. Blood Cells Mol Dis 38:287–293CrossRefPubMedGoogle Scholar
  5. Davies EH, Surtees R, DeVile C, Schoon I, Vellodi A (2007) A severity scoring tool to assess the neurological features of neuronopathic Gaucher disease. J Inherit Metab Dis 30:768–782CrossRefPubMedGoogle Scholar
  6. Dreborg S, Erikson A, Hagberg B (1980) Gaucher disease—Norrbottnian type. 1. General clinical description. Eur J Pediatr 133:107–118CrossRefPubMedGoogle Scholar
  7. El-Beshlawy A, Ragab L, Youssry I et al (2006) Enzyme replacement therapy and bony changes in Egyptian paediatric Gaucher disease patients. J Inherit Metab Dis 29:92–98CrossRefPubMedGoogle Scholar
  8. Erikson A (1986) Gaucher disease—Norrbottnian type (III). Neuropaediatric and neurobiological aspects of clinical patterns and treatment. Acta Paediatr Scand Suppl 326:1–42CrossRefPubMedGoogle Scholar
  9. Erikson A, Bembi B, Schiffmann R (1997) Neuronopathic forms of Gaucher′s disease. Baillieres Clin Haematol 10:711–723CrossRefPubMedGoogle Scholar
  10. Eto Y, Ida H (1999) Clinical and molecular characteristics of Japanese Gaucher disease. Neurochem Res 24:207–211CrossRefPubMedGoogle Scholar
  11. Grabowski GA (2005) Recent clinical progress in Gaucher disease. Curr Opin Pediatr 17:519–524CrossRefPubMedGoogle Scholar
  12. Grabowski G, Kolodny E, Weinreb N et al (2006) Gaucher disease: phenotypic and genetic variation. Chapter 146.1. The Online Metabolic & Molecular Bases of Inherited Disease. New York: McGraw-Hill Online:
  13. Ida H, Rennert OM, Iwasawa I, Kobayashi M Eto Y (1999) Clinical and genetic studies of Japanese homozygotes for the Gaucher disease L444P mutation. Hum Genet 105:120–126CrossRefPubMedGoogle Scholar
  14. Kaplan P, Andersson HC, Kacena KA, Yee J (2006) The clinical and demographic characteristics of non-neuronopathic Gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med 160:604–609CrossRefGoogle Scholar
  15. Khalifa AS, Fateen E, Tantawy AAG et al (1999) Phenotype-genotype expression of Gaucher disease in Egyptian infants and children. Egyptian J Pediatr 16:631–653Google Scholar
  16. Ludwig J (1979) Current methods of autopsy practice. Saunders, Philadelphia, PAGoogle Scholar
  17. STROBE statement. Strengthening the reporting of observational studies in epidemiology. Available at: Accessed 1 November 2008
  18. Tylki-Szymańska A, Czartoryska B (1999) Enzyme replacement therapy in type III Gaucher disease. J Inherit Metab Dis 22:203–204CrossRefPubMedGoogle Scholar
  19. Tylki-Szymańska A, Keddache M, Grabowski GA (2006) Characterization of neuronopathic Gaucher disease among ethnic Poles. Genet Med 8:8–15CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Anna Tylki-Szymańska
    • 1
  • Ashok Vellodi
    • 2
  • Amal El-Beshlawy
    • 3
  • J. Alexander Cole
    • 4
  • Edwin Kolodny
    • 5
  1. 1.Clinic of Metabolic Diseases, Endocrinology and DiabetologyThe Children’s Memorial Health InstituteWarsawPoland
  2. 2.Great Ormond Street Children’s Hospital NHS TrustLondonUK
  3. 3.Pediatric Hospital of Cairo UniversityCairoEgypt
  4. 4.Biostatistics/Epidemiology, Biomedical Data Sciences and Informatics, Genzyme CorporationCambridgeUSA
  5. 5.New York University School of MedicineNew YorkUSA

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