SICKLE-CELL-ANEMIA - BETA(S)-GENE CLUSTER HAPLOTYPES AS GENETIC-MARKERS FOR SEVERE DISEASE EXPRESSION

Identification of the beta(S) gene cluster haplotype and alpha-gene st atus provides a useful tool for the detection of high-risk patients wi th sickle cell anemia. Analysis of the relationship of the long-term c linical course to the above parameters has revealed that those with th e haplotype designated Senegal have decreased severity, those with the Benin haplotype have intermediate severity, and those with the Centra l African Republic (CAR) haplotype have the most severe clinical expre ssion. Further modulation of the clinical course occurs with the coinh eritance of alpha-thalassemia-2. In both Africa and the United States, the CAR beta(S) haplotype increased the risk (relative risk, 2.25; 95 % confidence interval, 1.41 to 3.87) of developing a complication and death at an early age. Detection of the CAR haplotype identifies the c hild with sickle cell anemia at risk for a rapid rate of progression o f sickle-induced microvasculopathy, ultimately leading to irreversible organ damage during the first three decades of life. In patients with the CAR haplotype, potential curative therapy, such as bone marrow tr ansplantation or gene insertion, should be seriously considered during childhood, before organ failure is clinically evident.