Clinical Utility of Confirmatory Genetic Testing to Differentiate Sickle Cell Trait from Sickle-β+-Thalassemia by Newborn Screening.

Lisa M. Shook,Charles T. Quinn,Deidra Haygood

doi:10.3390/ijns6010007

Abstract

Hemoglobin separation techniques are the most commonly used laboratory methods in newborn screening and confirmatory testing programs for hemoglobinopathies. However, such protein-based testing cannot accurately detect several hemoglobinopathies in newborns, especially when β-thalassemia mutations are involved. Here, we describe a consecutive cohort of newborns who were identified by newborn screening to have a likely diagnosis of sickle-β+-thalassemia (having an “FSA” pattern) who were determined to have sickle cell traits by confirmatory and genetic testing. We illustrate the clinical utility of genetic testing to make a correct and timely diagnosis in the setting of newborn screening for hemoglobinopathies.

Highlights

Hemoglobinopathies are a genetically complex group of blood disorders and the most commonly detected disorder overall by state newborn screening programs [1]
The benefits of universal newborn screening is that babies identified with sickle cell disease (SCD) can be enrolled in a comprehensive SCD program and that penicillin prophylaxis can be initiated promptly to significantly reduce morbidity and mortality [3,4]
On protein-based confirmatory testing at 2–4 weeks of age, 23/30 had an FAS pattern that indicated the correct diagnosis of HbAS, but 8/31 still had an FSA pattern consistent with

Summary

Introduction

Hemoglobinopathies are a genetically complex group of blood disorders and the most commonly detected disorder overall by state newborn screening programs [1]. Since 2006, in the United States, all babies are tested for hemoglobinopathies as part of universal newborn screening [2]. Newborn screening follow-up protocols typically include confirmatory testing, parental education, and genetic counseling, for babies with SCD. The benefits of universal newborn screening is that babies identified with SCD can be enrolled in a comprehensive SCD program and that penicillin prophylaxis can be initiated promptly to significantly reduce morbidity and mortality [3,4]. Protein-based testing for Hb disorders is used most commonly for both initial newborn screening and subsequent confirmatory testing. A limitation of protein-based testing is that it cannot accurately detect many types of hemoglobinopathies in newborns, when β-thalassemia mutations are involved

Methods

Results

Conclusion