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Keywords:

  • sickle cell disease;
  • infections;
  • anaemia;
  • α-thalassemia;
  • β-globin gene cluster haplotypes

Abstract: A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1±5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2±2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10–15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up >3 yr).

Epistatic mechanisms influencing SCD were studied. Coinherited α-thalassemia strongly reduced the risk of stroke (p<0.001) and increased that of painful crises (p<0.02). There was a low prevalence of Senegal and Bantu (CAR) βs-chromosomes in patients with meningitis (p<0.04) and osteomyelitis (p<0.03). Prevalence of Senegal βs-chromosomes was lower in the asymptomatic group of 27 patients (p<0.02). The patients come from a population of unmixed immigrants in whom the β-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the β-globin gene locus.