"Implementation of newborn screening for SCID is going slowly," agreed Dr. Watson. One challenge is the disparity of processes necessary for approval. Some states require legislative action, some need approval by the governor, and others require a go-ahead from the state’s department of health, which sometimes requires completion of a pilot program despite evidence collected from other states. Funding to properly outfit labs to carry out the new technology also can be a barrier.
Dr. Watson says that most of the states that initially began offering SCID screening already had the molecular assay technology in place from other programs, such as second-tier testing for cystic fibrosis. But even labs with the technical capability to conduct limited testing were not prepared to handle the high volume necessary for newborn screening. A possible cost-saving solution is that instead of having testing facilities available in every state, Dr. Watson suggests regionalized test centers, as is now done in New England, state partnerships, or even the use of commercial labs. Once a lab becomes equipped to handle SCID newborn screening, it often has the capacity to handle more than its own state’s needs, said Dr. Brower. Right now, Wisconsin and Massachusetts have the capacity to offer screening for other states.
Another limiting factor facing states considering adding SCID newborn screening can be the lack of a proper response mechanism. If a child screens positive for SCID, the child’s pediatrician must be prepared to shepherd the family through the next steps of diagnosis and arrange for immediate treatment, said Dr. Brower. To better inform pediatricians and other primary care physicians about SCID, the American College of Medical Genetics and Genomics offers an ACT sheet on SCID management aimed for the primary care provider. Dr. Watson also advises primary care providers to establish relationships with specialists in immunology, so that if a SCID baby is identified, the primary care provider can reach out for support regarding medical management, as well as for dealing with parental concerns.
The SCID newborn screening test is effective. Wisconsin was the first state to begin newborn screening for SCID. Between January 2008 and December 31, 2012, 5 infants with SCID or other forms of severe T-cell lymphopenia were detected out of almost 208,000 infants screened. No infants with SCID were missed during the screening period. The specificity of the assay used was 99.98%, with a false-positive rate of 0.018%. (Pediatrics 2012;130:S50-1). In California, the test had 99.91% specificity. Of 11 infants identified with SCID, all were able to be treated, with more than 90% alive at 6-21 months. In Colorado, a child with SCID was identified within the first week the SCID screening program began.
As part of the ACMG, the NBSTRN (www.nbstrn.org) maintains several SCID resources for investigators, including links to patient registries, a virtual repository of dried blood spot samples, and a longitudinal pediatric data resource. It also was involved with the National SCID Pilot Study that screened newborns in California, Louisiana, New York, and Puerto Rico. The ACMG operates the NBSTRN as part of funding it receives from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for research into new therapeutics, technologies, and other aspects of newborn screening.
The NBSTRN also holds monthly conference calls for stakeholders, including scientists, clinicians, public health specialists, administrators, and patient advocates, to discuss SCID-related developments. "After decades of living with SCID children, some of whom we have already lost, mothers with children like mine who are older and were late transplants understand the urgency. They push us to think, what else can we be doing?" said Dr. Brower. Those interested in helping to broaden SCID screening may consult the Immune Deficiency Foundation’s SCID Newborn Screening Toolkit for Advocates or attend its national conference in Baltimore on June 27-29.
Screening for SCID
SCID is a group of conditions characterized by blocks in T-cell development, leading to functional deficiencies in both T cells and B cells.
Fortunately, a screening test able to detect low levels of a DNA biomarker of normal T-cell development has proven successful at identifying individuals before symptoms appear. The test, developed by Dr. Jennifer M. Puck of the University of California, San Francisco, measures T-cell receptor excision circles (TRECs) using a polymerase chain reaction (PCR) process in samples of dried blood spots commonly taken from infants that are used for other screening purposes. Infants with SCID or related disorders have very low or undetectable levels of TRECs.
Being able to measure TRECs "was a real game changer for SCID," said Dr. Brower. It fit well into ongoing public health programs that utilized dried blood spot collections. "This was a technology developed at [the National Institutes of Health] that was developed and translated into clinical care with clear public health benefits." At the NBSTRN, Dr. Brower leads similar efforts to take genomic advances from bench to bedside.