Phenotype and mutational spectrum in Tunisian pediatric gaucher disease


Hadhami Ben Turkia
Imen Riahi
Hatem Azzouz
Saloua Ladab
Wafa Cherif
Amal Ben Chehida
Mohamed S. Abdelmoula
Catherine Caillaud
Jalel Chemli
Sonia Abdelhak
Neji Tebib
Marie F. Ben Dridi


Background: Gaucher disease (GD) is a sphingolipidosis with heterogeneous phenotypic expression. The vital and / or functional prognosis may be threatened by an early visceral severe involvement in type 1 or a neurological degeneration in the more rarest neuroneupathic forms. The phenotypic and genotypic data regarding Gaucher disease are poorly known in Maghrebian countries; they are even less for pediatric forms. The aim of the study is to highlight the specific phenotypic and genotypic changing among the widest Gaucher pediatric cohort in the Tunisian population. Methods:a restrospective study of a sample oh children in voluved by gaucher disease.
Results: Twenty one cases of GD were identified, divided into 13 cases with type 1, 5 with type 3 and 3 children with acute neurological form. The first symptoms occurred before 1 year age in one third of patients with type 1GD. The clinical phenotype was severe according to the high severity score index and proportion of growth retardation. Portal hypertension was found in 8 patients. Three type 3 GD patients died before occurrence of the neurological signs. The phenotype was intermediate between the classic type 2 GD and its perinatal lethal variant. Three patients were treated with enzyme replacement therapy and 4 others had allogenic bone marrow transplantation with a favorable outcome. Three mutations dominate the genotypic spectrum of GD in this cohort. Additionally to the N370 mutation, L444P and RecNciI mutations seem to occur more frequently compared to the GD forms presenting in adulthood.
Conclusion: This data confirm the particular severity of Gaucher disease manifesting in childhood. This was enhanced through the high frequency of severe mutations. Further studies on largest cohort are needed to more clarify the phenotypic and genotypic features of Gaucher disease in Tunisia.



Gaucher disease, Childhood, Genotype, Bone marrow transplantation, Enzymatic replacement therapy



  1. Beutler E, Grabowski GA. Gaucher disease. In Scriver C, Beaudet A, Valle D, Sly W editors. The metabolic and molecular bases of inherited disease.8th ed. 2001 New York: McGraw-Hill: 3635-68.
  2. Germain DP. Gaucher disease: clinical, genetic and therapeutic aspects. Pathol Biol 2004; 52:343-50.
  3. Charrow J, Andersson HC, Kaplan P et al. The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease Arch Intern Med. 2000 ;160 :2835-43
  4. Charrow J, Andersson HC, Kaplan P et al. Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr. 2004;144:112-20
  5. Kaplan P, Mazur A, Manor O, Charrow J, Esplin J, Gribble TJ, Wappner RS, Wisch JS, Weinreb NJ. Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase J Pediatr. 1996;129:149-53
  6. W. Cherif, H. Ben Turkia, N. Tebib, O. Amaral, F. Ben Rhouma, M.S. Abdelmoula H. Azzouz, E. Barkaoui, C.Caillaud, M.C. Miranda, S. Abdelhak, M.F. Ben Dridi Mutation Spectrum Of Gaucher Disease In Tunisia :High Prevalence Of Heterozygote Composite N370s/Rec NciI. Arch Inst Pasteur Tunis.2007;84:65-70
  7. Zimran A, Sorge J, Gross E, Kubitz M, West C, Beutler E. Prediction of severity of Gaucher's disease by identification of mutations at DNA level. Lancet. 1989; 12:349-52.
  8. Stirnemann J, Caubel I, Kettaneh A, Fain O, Belmatoug N. Epidemiologic, clinical, biological and therapeutic aspects of Gaucher disease Presse Med. 2003; 32:503-11
  9. Caubel I, Billette de Villemeur T, Belmatoug N. Comité d'étude du traitement de la maladie de Gaucher. Gaucher's disease in children: first clinical signs, natural course and benefits of enzyme replacement therapy. Arch Pediatr. 2003;10:681-8
  10. Levrat V, Forest I, Fouilhoux A, Guffon N. Gaucher disease in childhood Rev Med Interne. 2007 Oct;28 (Suppl 2):S183-6
  11. Beutler E, Demina A, Laubscher K et al. The clinical course of treated and untreated Gaucher disease. Astudy of 45 patients. Blood Cells Mol Dis. 1995; 21:86-108.
  12. Kolodny EH, Ullman MD, Mankin HJ, Raghavan SS, Topol J, Sullivan JL. Phenotypic manifestations of Gaucher disease: clinical features in 48 biochemically verified type 1 patients and comment on type 2 patients. Prog Clin Biol Res. 1982; 95:33-65
  13. Sidransky E, Tayebi N, Ginns EI.Diagnosing Gaucher's disease: early recognition, implications for treatment and genetic counseling. Clin Pediatr (Phila) 1995; 34:365-71.
  14. Zevin S, Abrahamov A, Hadas-Halpern I, Kannai R, Levy-Lahad E, Horowitz M, Zimran A.Adult-type Gaucher disease in children: genetics, clinical features and enzyme replacement therapy. Q J Med. 1993;86:565-73
  15. Choulot JJ, Bargiarelli M, Saint-Martin J. Portal hypertension complicating Gaucher's disease Arch Fr Pediatr. 1981; 38:267-8.
  16. James SP, Stromeyer FW, Chang C, Barranger JA Liver abnormalities in patients with Gaucher's diseaseGastroenterology. 1981;80:126-33
  17. Aderka D, Garfinkel D, Rothem A, Pinkhas J. Fatal bleeding from esophageal varices in a patient with Gaucher's disease. Am J Gastroenterol. 1982;77:838-9
  18. Perel Y, Bioulac-Sage P, Chateil JF, Trillaud H, Carles J, Lamireau T, Guillard JM Gaucher's disease and fatal hepatic fibrosis despite prolonged enzyme replacement therapy Pediatrics. 2002;109:1170-3
  19. Gürakan F, Terzio€lu M, Koçak N, Yüce A, Ozen H, Ciliv G, Emre S Analysis of three mutations in Turkish children with Gaucher disease J Inherit Metab Dis. 1999;22:947-8
  20. Drugan C, Procopciuc L, Jebeleanu G, Grigorescu-Sido P, Dussau J, Poenaru L, Caillaud C Gaucher disease in Romanian patients: incidence of the most common mutations and phenotypic manifestations Eur J Hum Genet. 2002; 10:511-5
  21. Filocamo M, Mazzotti R, Stroppiano M, Seri M, Giona F, Parenti G, Regis S, Corsolini F, Zoboli S, Gatti R Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients Hum Mutat. 2002;20:234-5
  22. Erdos M, Hodanova K, Taskó S, Palicz A, Stolnaja L, Dvorakova L, Hrebicek M, Maródi L Genetic and clinical features of patients with Gaucher disease in Hungary Blood Cells Mol Dis. 2007;39:119-23
  23. Goker-Alpan O, Hruska KS, Orvisky E, Kishnani PS, Stubblefield BK, Schiffmann R, Sidransky E Divergent phenotypes in Gaucher disease implicate the role of modifiers J Med Genet. 2005; 42:e37