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Molecular characteristics of pediatric patients with sickle cell anemia and stroke
1Children's Hospital of Michigan and the Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USA.
Insights
Cerebrovascular accidents (CVA) in children with sickle cell anemia (SS) may be more common in females and those with specific beta(S) haplotypes. Alpha-gene deletion appears protective against CVA in these young patients.
Area of Science:
- Pediatric Hematology
- Neurology
- Genetics
Background:
- Cerebrovascular accidents (CVA) are significant complications in children with sickle cell anemia (SS).
- Risk factors predisposing children to CVA in SS are not well-established.
- Understanding these factors is crucial for early detection and prevention strategies.
Purpose of the Study:
- To investigate the association between alpha-globin genotype, beta(S) haplotype, and CVA in children with SS.
- To identify specific genetic factors that may predispose or protect against CVA in this pediatric population.
Main Methods:
- Analysis of alpha-globin genotype and beta(S) haplotype in 41 children with SS who experienced CVA.
- Comparison of genetic findings with a larger cohort of children with SS.
- Retrospective review of patient data, including age at stroke and gender distribution.
Main Results:
- Alpha-gene deletion was less prevalent (19.5%) in children with CVA compared to the general African-American population.
- Certain beta(S) haplotypes (Ben/CAR, Ben/Ben, Ben/Sen, CAR/CAR) were more common in patients with CVA.
- CVA occurred more frequently in females and in neonates with four or more alpha-genes and specific beta(S) haplotypes (Ben/CAR, atypical, CAR/CAR).
Conclusions:
- Alpha-gene deletion may offer a protective effect against CVA in children with SS.
- Specific beta(S) haplotypes are associated with an increased risk of CVA in pediatric SS patients.
- Females and neonates with specific genetic profiles (e.g., four alpha-genes, certain beta(S) haplotypes) appear to be at higher risk.
Abstract:
Cerebrovascular accidents (CVA) are serious complications of sickle cell anemia (SS) in children. Factors that predispose children to this complication are not well established. In an effort to elucidate the risk factors associated with CVA in SS, we have determined the alpha-globin genotype and the beta(S) haplotype of children with this complication. Among 700 children with SS followed at Children's Hospital of Michigan, 41 (6%) are on chronic transfusions because of stroke due to cerebral infarction. The mean age of patients with CVA at the time of stroke was 5.6 +/- 3.2 years (mean +/- SD). The male/female ratio was 2/3. Only 8 of 41 patients (19.5%) had one alpha-gene deletion, compared to the reported prevalence of 30% in African-Americans. None of the patients had two alpha-gene deletions, and two (5%) had five alpha-genes. These findings are different than those in our adult patients with SS, where the prevalence of -alpha/-alpha and alphaalphaalpha/alphaalpha is 4% and <2%, respectively. Ten different beta(S)-haplotypes were detected in the patients studied. The majority of the patients (31%) were doubly heterozygous for the Ben/CAR haplotypes followed by Ben/Ben, Ben/Sen, and CAR/CAR haplotypes, respectively. The prevalence of these haplotypes, with the exception of the CAR/CAR haplotype, was higher in females than males. All the patients with CAR/CAR haplotype were males, had four alpha-genes, and ranked third in prevalence. Three patients were heterozygous for the Cameron haplotype. The Cameron and atypical haplotypes were more prevalent than reported in patients with SS at large. The data suggest that CVA in children seems to occur more frequently in females and in patients with certain beta(S) haplotype. alpha-Gene deletion seems to offer a protective effect against this complication. Neonates with four or more alpha-genes whose beta(S) haplotype 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 with or without CVA may clarify this issue.