Abstract
Sickle cell disease (SCD) is a group of related yet genetically complex hemoglobinopathies. Universal newborn screening (NBS) for SCD is performed in the United States and many other nations. Classical, protein-based laboratory methods are often adequate for the diagnosis of SCD but have specific limitations in the context of NBS. A particular challenge is the differentiation of sickle cell anemia (SCA) from the benign condition, compound heterozygosity for HbS and gene-deletion hereditary persistence of fetal hemoglobin (HbS/HPFH). We describe a sequential cohort of 44 newborns identified over 4.5 years who had molecular genetic testing incorporated into NBS for presumed SCA (an “FS” pattern). The final diagnosis was something other than SCA in six newborns (12%). Three (7%) had HbS/HPFH. All had a final, correct diagnosis at the time of their first scheduled clinic visit in our center (median 8 weeks of age). None received initial counseling for an incorrect diagnosis. In summary, genetic testing as a component of NBS for SCD is necessary to provide correct genetic counseling and education for all newborns' families at their first visit to a sickle cell center. Genetic testing also permits the use of early, pre-symptomatic hydroxyurea therapy by preventing infants with HbS/HPFH from receiving unnecessary therapy. We argue that genetic testing should be incorporated into contemporary NBS for SCD.
Highlights
Sickle cell disease (SCD) is the name for a group of related hemoglobinopathies that affects numerous populations worldwide. It is a monogenic disease caused by mutations of the β-globin gene (HBB), there are a number of distinct genotypes of SCD that require differentiation to inform clinical care
The most common and severe form of SCD is the homozygous state for the sickle hemoglobin (HbS) mutation, called sickle cell anemia (SCA) or HbSS
The overall goal of this newborn screening (NBS)-based genetic testing is to differentiate HbSS from HbS/HPFH before affected newborns have their first visits in our comprehensive sickle cell center
Summary
Sickle cell disease (SCD) is the name for a group of related hemoglobinopathies that affects numerous populations worldwide. A watch-and-wait approach was reasonable given the limited and usually delayed initiation of treatment options The hazards of this approach include unnecessary venipunctures, clinic visits, and prophylactic antibiotics for the children with HbS/HPFH and anxiety and fear about a serious disease, incorrectly diagnosed, for their parents and family. We describe a sequential cohort of newborns who had a presumed diagnosis of SCA by NBS (an “FS” pattern), several of whom had HbS/HPFH or other forms of SCD that were correctly and rapidly diagnosed by genetic testing before the child’s first visit to our center, thereby preventing incorrect counseling and unnecessary medical interventions. The overall goal of this NBS-based genetic testing is to differentiate HbSS from HbS/HPFH before affected newborns have their first visits in our comprehensive sickle cell center.
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