Newborn screening for hemoglobin disorders

The epidemiology of hemoglobinopathies in the United States reflects recent changes in the demographic make-up of the country's population. The incidence of thalassemias, in particular, has risen in parallel with immigration of high-risk populations. With an increase in Asian immigration by 2000% in the past three decades, hemoglobinopathies such as Hb H (β4) and Hb E-β-thalassemia (β-thal) have acquired proportionally greater clinical significance in several states, including California. Newborn screening (NBS) for hemoglobinopathies allows for the identification of affected individuals so that prophylactic treatment and comprehensive care may be provided prior to the development of clinical complications. Although the more common hemoglobin (Hb) variants, such as Hb S or Hb C, are readily identified by NBS programs, other clinically significant Hb disorders often remain unresolved or are not reported by NBS programs. The state of California mandates NBS and follow-up for thalassemic disorders as well as sickle cell disease. A centralized laboratory for diagnostic testing and rapid reporting of NBS results is a necessary component of a comprehensive NBS program. Confirmatory diagnostic testing for the California NBS program is provided by the Hemoglobinopathy Reference Laboratory at Children's Hospital & Research Center Oakland (CHRCO), Oakland, CA, USA. Using electrophoresis, high performance liquid chromatography (HPLC) and DNA-based methods, the laboratory annually performs diagnostic testing for sickle cell disease, β-thal and Hb H disease on more than 1,000 samples. While most screening results are straightforward, 5% of newborns identified with a presumptive hemoglobinopathy by primary screening are modified after confirmatory testing. The availability of rapid and reliable genotyping assays to complement traditional protein chemistry methods for hemoglobinopathy screening has facilitated the diagnosis of thalassemias and sickling disorders in newborns with ambiguous screening results. Together with coordinated follow-up systems in place, the Hemoglobinopathy Reference Laboratory has contributed to the success of the NBS program in the rapid identification and delivery of care to newborns with clinically significant Hb disorders.