For decades, Dr. Jennifer Puck, a professor of pediatrics at UCSF, has been a leading advocate for universal newborn screening to identify Severe Combined Immunodeficiency (SCID). Children with SCID, also known as bubble baby disease, are born without a working immune system, making them vulnerable to severe complications from even mild infections like the common cold. Early detection of SCID is crucial to begin treatment before infections occur.
Dr. Puck’s Work in Newborn Screening for SCID
Dr. Puck first created and developed the TREC (T cell receptor excision circle) newborn screening test for SCID in 2005 while working as a scientist at the National Human Genome Research Institute at the NIH. She had collaborated with people who took care of SCID patients, and enrolled SCID families in gene mapping studies. In order to find a cost-effective way to screen babies for SCID, Dr. Puck thought of using TRECs obtained from dried blood spots. Vicki and Fred Modell encouraged her and supported the work from the start.
The TREC test identifies a deficiency of T cells, which are essential for fighting infections, using DNA isolated from the dried bloodspots routinely collected from newborns for various health screenings. Dr. Puck moved to California in 2006 and, again working with the Modell's, helped convince state lawmakers to require the test statewide. In 2009 Dr. Puck conducted a prospective research study of newborn screening for SCID in two hospitals on the Navajo Nation in Arizona, where a high incidence of SCID occurs due to a founder mutation. Her main purpose was to demonstrate that the TREC assay could be successfully added to existing newborn screening tests, as well as to inform the Navajo people about SCID and explain to them that the TREC test is not a genetic test, but rather an indicator of low T cells due to any cause. With successful results of Dr. Puck’s studies along with pressure from patients and pilot programs in Wisconsin and Massachusetts newborn screening for SCID was adopted in California in 2010, and other US states began adopting the test. All 50 states had added SCID screening as part of their standard newborn panel by the end of 2018.
The Primary Immune Deficiency Treatment Consortium (PIDTC) has been collecting data from SCID cases at 47 different centers across the US and Canada since 2009, including retrospective data back to 1982. This data showed that there was no improvement in the survival rate for SCID until 2010-2018, as newborn screening was being implemented. This study, published in The Lancet in 2023 by Monica Thakar and the PIDTC SCID investigators with leadership from Dr. Puck showed a direct survival benefit of SCID screening, which is normally extremely difficult for population-based screening programs to prove. Survival rates are now higher for babies with SCID because they are diagnosed early.
Dr. Puck’s Hope for the Future
Many of those in the Primary Immunodeficiency (PI) community question why newborn screening can’t be implemented for other forms of the disease, such as XLA, CVID, etc. Scientists have been working to come up with an easy, sensitive and specific cost-effective test (like the TREC test) to screen for other forms of PI. The TREC test itself is limited because it looks only at T-cell development, so it cannot test for other forms of PI. The B-cell marker, KRECs, has been proposed to detect absent B cells in newborns. This field is evolving, and immunologists are now looking into genomic sequencing as a potential screening tool; however, the population diversity is so large that many variants in sequence cannot yet be interpreted. The price of this kind of test would also not be cost-effective with current technology. Dr. Puck’s hope for the future is for more bright, creative minds to continue entering this field of study to investigate how early diagnosis could be accomplished for many other forms of PI. She encourages families of known PI cases to have their relatives get genetic testing, as this would put us further ahead of where we are now.
Dr. Puck also hopes the Lancet study mentioned above will persuade more countries outside of the US to adopt newborn screening for SCID. You can read more about the study here.