Development of Population-Based Newborn Screening for Severe Combined Immunodeficiency

Abstract

Purpose of the Study. To evaluate analysis of T-cell development as a potential population-screening method for severe combined immunodeficiency (SCID). Study Population. Twenty-three infants with SCID, 2 patients without SCID, 245 randomly selected infants, and several healthy adults. Methods. DNA was extracted from dried blood spots on standard newborn screening (Guthrie) cards. The DNA was subjected to polymerase chain reaction (PCR) to amplify and quantitate the number of T-cell receptor excision circles (TRECs), a marker of T-cell development in the thymus. For comparison, the β-actin gene was also amplified by PCR. Results. None of the SCID patients’ blood spots contained detectable TRECs, whereas the infants without SCID had normal TRECs. Healthy adults had normal TRECs, and intentional depletion of T cells led to the disappearance of TRECs in simulated blood spots. Approximately 3% of randomly collected blood spots did not contain measurable TRECs but did contain β-actin. Conclusions. Measurement of TRECs by PCR can accurately identify infants with SCID. The relatively high percentage (3%) of screened spots having the SCID profile indicates the need for further refinement of the method before a larger population study. Reviewer Comments. Newborn screening for SCID is desirable because of the rapidly fatal nature of this disease and because of the good outcomes that may be obtained with the earliest possible diagnosis. The minimum estimate of the incidence of SCID is >1 per 100 000 births, comparable to other diseases that are already part of newborn screening programs. Almost all patients with SCID lack detectable TRECs. The ability to accurately measure them in dried blood spots represents a tremendous advance toward the possibility of effective newborn screening for this genetically very heterogeneous group of disorders. If the specificity of the analysis can be improved, this may soon be implemented in newborn screening programs.