Foreword

Article Outline

• Copyright

In this issue of Current Problems in Pediatric and Adolescent Health Care, Dr. Rupa Redding-Lallinger and Dr. Christine Knoll from the University of North Carolina at Chapel Hill provide a thorough review of sickle cell disease, the most common inherited blood disorder in the United States. Until recently, people with sickle cell disease often did not survive childhood. But there have been impressive advances in the last 25 years. I’ve just returned from Bethesda where I attended a 1-week short course in genomics at the National Human Genome Research Institute. The term genomics refers to a “scaled-up” version of genetics research in which scientists can look at all of the genes in a living creature at the same time. The amount that has been learned about sickle cell disease through genomic research in the last decade is phenomenal and has the potential to transform the way we practice pediatrics.

Gene therapy is one example. You probably recall that several years ago researchers at Harvard created mice with a human gene that produces hemoglobin S. They then removed bone marrow from the mice and genetically corrected it by adding the anti-sickling human beta-hemoglobin gene and transplanted the corrected marrow into other mice with sickle cell disease. When the genetically corrected mice began producing high levels of normal red blood cells and showed a dramatic reduction in sickled cells, there was great hope that gene therapy could cure sickle cell disease in children. So far, this hope has not been realized, but research is continuing and researchers are beginning to gain more understanding of the short and long term toxicity of gene therapy.

Another example is the use of DNA analysis to inform clinical practice. Pediatricians have long known that certain children with sickle cell disease have relatively few problems while other children with the identical genotype have numerous medical complications. It appears that modifier genes may determine the severity of a child’s disease. These modifiers include the beta-globin genotype, fetal hemoglobin, beta S gene cluster haplotype, alpha-thalassemia, and modifiers related to risk of stroke. In the not-too-distant future, clinicians may be able to tailor treatment and prevention efforts for children with sickle cell disease based on the individual child’s DNA, so that children with modifier genes putting them at high risk of complications such as stroke are offered special preventive measures.

After reading this month’s issue, I hope that you’ll appreciate the major advances and continued challenges in caring for children with sickle cell disease.