Though symptomless at birth, infants with severe combined immunodeficiency disorder (SCID) are at high risk for developing infections that they are unable to fight off, often leading to death before the age of two. Fortunately, the genetic disorder is treatable by hematopoietic stem cell transplantation if it is diagnosed early enough, and Dr. Mary Beth Fasano from the Division of Immunology has made it her goal to streamline the diagnostic process by helping to develop and improve newborn SCID screening now mandatory statewide.
Serving as a medical consultant for the Iowa Newborn Screening Program, Dr. Fasano, who also directs the Pediatric Immune Disorder Clinic at University of Iowa Children’s Hospital, has assisted on the administrative and clinical end of piloting and launching the screening in Iowa, which went live in July 2014. Since then, she has worked to further the reach of the screening by sharing Iowa’s experience in SCID newborn screening with the Dakotas. Despite the difficulty in navigating the differences in states’ funding and insurance policies, North Dakota will officially begin screening for SCID this July.
Newborn screening is not a particularly new practice—for decades, blood samples from newborns have been sent to state laboratories to screen for numerous disorders. But the addition of SCID to the list has been such a growing concern among immunologists and pediatricians in recent years that almost all states now require it.
“It really is a mix of public engagement and clinical practice. And that’s probably one of the things that I really like about the job, is that it’s a huge public health initiative which can save lives and improve the quality of life for these babies that are born with this life-threatening immune deficiency,” Dr. Fasano said. “It can also save huge amounts of healthcare dollars with early identification and early treatment before these babies become quite sick.”
Though the nationwide requirement of SCID screening may seem to be the end of the road, Dr. Fasano still sees room for improvements in the screening process. For instance, many premature infants return abnormal screenings because the thymus has not developed enough to produce and mature the T lymphocytes picked up by the assay to ensure proper immune function. Given an abnormal screening, the sample goes into second-tier testing using flow cytometry, which counts the absolute number and relative percentages of these different types of lymphocyte white blood cells. The current issue with the second-tier testing, Dr. Fasano says, is that there are limited published normative ranges for lymphocytes in premature infants.
“Working along with Emily Phillips in the Iowa Newborn Screening Program, and Sergei Syrbu and colleagues in Immunopathology here at UI, we are getting them cord-blood samples from the babies born here at various gestational ages, and then the flow lab is actually running tests to determine for our University of Iowa flow cytometry lab what normative ranges are,” Dr. Fasano said. “I think that is something that will really help University of Iowa, because it’s really going to be data unique to our machinery and pathology team here.”
The screening assay developed for SCID may also help identify babies with other inherited disorders associated with T-cell lymphopenia. Dr. Fasano reports that Iowa’s screening program has identified babies with DiGeorge syndrome, Trisomy 21, Jacobsen syndrome, and complex congenital heart disease. “The exciting thing is that that may help us to learn more about basic thymic development. It may help us to identify babies who have other disorders, which, although it’s not SCID and they don’t need transplantation, they can get into treatment earlier,” she said.
The passion Dr. Fasano carries for her work shows not only in the progress made in the past years, but in her attitude toward the work itself: “I love it, being a clinician and an allergist/immunologist who sees primary immune deficiency, but also the opportunity to oversee, administrate, and be involved in an important public health initiative. I hadn’t anticipated how rewarding that part might be, but it really has been.”
For the future, Dr. Fasano has hopes that a standardized national database and registry will be developed to include protocols for the evaluation and management of babies with T-cell lymphopenia identified by SCID newborn screening. “They still cannot tell individual states how to fund or do your actual testing,” she said, “but it may be able to get the medical consultants together as a group, and assure that there’s maybe some uniformity there. I think that that has huge value for improving patient outcomes.”