Phenotype and mutational spectrum in Tunisian pediatric Gaucher disease

Gaucher disease [GD] is a sphingolipidosis with heterogeneous phenotypic expression. The vital and/or functional prognosis maybe threatened by an early visceral severe inolvement 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 study is to highlight the specific phenotypic and genotypic changing among the widest Gaucher pediatric cohort in the Tunisian population. A restrospective study of a sample of children involved by gaucher disease. 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 2GD 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 RecNcil mutations seem to occur more frequently compared to the GD forms presenting in adulthood. 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

[Enzyme replacement therapy for gaucher pardiatric disease: the only Tunisian Experience]

We report through the first Tunisian experience with enzyme replacement therapy, the goals and consensus recommendations for treatment and monitoring of paediatric non neuronopathic Gaucher disease. Three children with Gaucher disease undergone enzyme replacement therapy with Cerezyme for severe visceral and/or bone involvement. Visceral, hematologic, bone, and growth parameters were assessed initially and under treatment. Two children presented with severe visceral or hematologic picture. One patient had myocardiopathy and primitive portal hypertension and another was diagnosed with cirrhosis related to Gaucher disease. Recurrent avascular necrosis and osteoporosis have justified treatment in another child. All patients received an initial dose of 60U/Kg/2 weeks. We have seen a gradual disappearance of hepatosplenomegaly and a rapid normalisation of hematological parameters in two patients. A resistance to treatment indicated splenectomy in one patient. The improvement in bone mineral density was slower. A significant growth gain was observed in patients with growth retardation. No patient had developed Cerezyme antibodies. Despite its effectiveness and safety demonstrated in these children, enzyme replacement therapy remains inaccessible because of its cost for emerging countries. The allogeneic bone marrow is an alternative therapy to encourage and to propose precociously for severe paediatric forms of Gaucher disease