Molecular characteristics of pediatric patients with sickle cell anemia and stroke

Cerebrovascular accidents (CVA) are serious complications of sickle cell an emia (SS) in children, Factors that predispose children to this complicatio n are not well established. In an effort to elucidate the risk factors asso ciated with CVA in SS, we have determined the alpha -globin genotype and th e beta (S) haplotype of children with this complication. Among 700 children with SS followed at Children's Hospital of Michigan, 41 (6%) are on chroni c transfusions because of stroke due to cerebral infarction. The mean age o f patients with CVA at the time of stroke was 5.6 +/- 3.2 years (mean +/- S D). The male/female ratio was 2/3. Only 8 of 41 patients (19.5%) had one al pha -gene deletion, compared to the reported prevalence of 30% in African-A mericans. None of the patients had two alpha -gene deletions, and two (5%) had five a genes. These findings are different than those in our adult pati ents with SS, where the prevalence of -alpha/-alpha and alpha alpha alpha/a lpha alpha is 4% and <2%, respectively. Ten different Ps-haplotypes were de tected in the patients studied. The majority of the patients (31%) were dou bly heterozygous for the Ben/CAR haplotypes followed by Ben/Ben, Ben/Sen, a nd CAR/CAR haplotypes, respectively. The prevalence of these haplotypes, wi th the exception of the CAR/CAR haplotype, was higher in females than males . All the patients with CAR/CAR haplotype were males, had four cw-genes, an d ranked third in prevalence. Three patients were heterozygous for the Came ron haplotype. The Cameron and atypical haplotypes were more prevalent than reported in patients with SS at large. The data suggest that CVA in childr en seems to occur more frequently in females and in patients with certain b eta (S) haplotype. alpha -Gene deletion seems to offer a protective effect against this complication. Neonates with four or more cu-genes whose PS hap lotype is Ben/CAR, atypical, or CAR/CAR seem to be at a higher risk for CAV than other patients. A prospective study on a larger group of patients wit h or without CVA may clarify this issue. (C) 2001 Wiley-Liss, Inc.