Contribution to the Natural History of Sickle Cell Disease in DR Congo B. Ngasia, G. Kazadi, A. Okakesema, LM. Aissi, S. Wembonyama, L.Tshilolo

Introduction DRC, is an enclosed French country speaking in Central Africa with the particularlity to present a genetic homogeneous population of 68 millions whose 25 to 30 % of adults AS and 2 % newborns SS SCD is characterized by a variable phenotype expression depending on genetic and environmental factors. The more severe form seems to be related to people bearing the Bantu’s haplotype.

The aim of our project was To contribute to the description of the natural history of SCD in DRC : by determining the prevalence of beta S gene by determining the specific clinical and biological data in Congolese SCA patients

Material and methods Newborn screening of SCA was performed by IEF and Capillary electrophoresis in partnership with 48 maternity Clinical and biological parameters were regularly determined in the course of the follow up of patients in Kinshasa and provinces.

Results and impact of the actions 1° Prevalence of beta S gene: – In newborns: 58,000 : 16% were AS and 1.68 %SS. – Prevalence of AS trait in general population: 25% -ethnic distribution and the impact of malaria on betas S gene distribution (L. Tshilolo and all. J Clin Pathol. 2009; 62(1):35-8) 2°specific clinical: Blood transfusion rates was at 80 % in reduced to 40% with the introduction of a a comprehensive SCA managment program High risk of contamination by viral infections (HIV, VHB and VHC) was also reduced from 15% to 5 % (L. Tshilolo and all. Indian J Pediatr2007;74(8): ).

Specific clinical features in Congolese SCA Hand foot syndrome : was the early clinical signs in >60 % of cases. Torrential nose bleeding: 30% of cases in children>5 yrs Tooth decay and hypertrophic tonsillitis were frequent in young patients. Osteomyelitis ( salmonella)was severe and often with multiple localization. (Arch Pédiatr 1996 : 3 ; ; Développement et Santé 2006 ; 182 : 13-19; Med Afr Noire, 2003 ; 50(12) : )

Hepato-splenomegaly Large spleen observed in 40% Persistent after 5yrs of age Related to malaria? Alpha –thalassemia ? Hepatomegaly Viral infections? Iron hyperloading?

Most of the Congolese SCA patients (92%) bear the bantu’s haplotype. α-thal deletion (3.7pdb) was observed in 39.5% of SS and 44.8% of AS. – Among the AS, there was a trimodal distribution percentage of HbS corresponding to 2,3 and 4 α genes. (Nouv Rev Fr Hematol 36(1), feb 1994). Biological and genetics data

Impact of alpha Thal on HbS concentration Data from DRC

Congolese SCA patients displayed a permanent inflammatory and undernutrition status (Ann Biol Clin 2009; 67 (6): 1-6) and developed high titers of autoantibodies (J Rheumatol 2011;38:302–9).

Humoral immunity hyperstimulation in SCA patients Reduction of the haptoglobine/A1GP ratio: constant hemolytic status (NO déficit) Hypergamma-globulinemie in children with SCA is associated to a permanent inflammatory status

What were Hematologic parameters? In steady state, displayed a mean value of: Hb at 7.2 g/dl, Hct 23.1%, red cells: 2.47 tera/L and reticulocytes at 8.8%; a leucocytosis (14.9 g/L) associated with eosinophilia (7.8%) and monocytosis (14%); VGM: 95.3 fL; CCMH:30.3% L and platelets: giga/L. Mean HbF level was at 7.2% (LT shilolo, Med Trop 2010; 70: 459 – 463)

Mean values of F-cells in SCA patients were 5.4% SCA patients with F cells>4.5% developed less painful crisis and displayed higher number of reticulocytes.

Conclusion Knowledge of the natural history of SCD is one of the main step for research progress and sustainability of various projects on SCD control in Central Africa. These results are a booster for a large study of the role of environmental and genetic factors in the high variability of the SCD phenotype

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