the AJMG SEQUENCE
More states screen for severe combined immunodeficiency
Screening finds other genetic syndromes marked by immunodeficiency
Two years after the US Department of Health and Human Services recommended that states add severe combined immunodeficiency disorder (SCID) to their newborn screening panels, Texas and Florida plan to join a growing number of states in making screening for the often-fatal disorder mandatory.
Newborn screening for SCID represents states' first forays into screening for immune system disorders, say state newborn screening directors and immunologists who treat the disease. “SCID brings immune deficiency into the realm of screening, and there are many inherited problems of the immune system,” says immunologist Jennifer Puck, MD, Professor of Pediatrics, University of California San Francisco. Dr. Puck first suggested to the Department of Health and Human Services that it add SCID to its list of diseases recommended for state newborn screening panels.
Newborns in Wisconsin, Massachusetts, California, New York, Michigan, Colorado, Mississippi, and Delaware currently receive SCID screening, while Illinois and West Virginia are planning to provide the screening. At press time, Minnesota was planning to implement universal newborn SCID screening on August 1. Meanwhile, Louisiana's pilot SCID screening program has ended, and the state's newborn screening program is awaiting legislation on funding for resumed SCID testing.
Prior to statewide newborn screening for SCID, immunologists who saw infants with SCID almost always encountered very ill children with opportunistic infections and failure to thrive. “Many families had to experience a tragic loss of a first infant with SCID in order to be prepared to diagnose and treat a second one in a timely fashion. Today, we're seeing some happy, bouncy babies found by screening before they get sick,” says Dr. Puck.
Finding SCID and More
Known mutations in 14 different genes cause SCID. Newborn screening programs currently test for SCID using T-cell receptor excision circle (TREC) assays, which identify infants with absent or extremely low number of T cells. These include newborns with SCID of all genetic causes. Screening can help identify babies with other conditions characterized by low T cells, as well.
Since Wisconsin became the first state to screen newborns for SCID in 2008, states have found immune deficiencies in infants with other inherited disorders. While immunodeficiency was a known feature of velo-cardio-facial/DiGeorge syndrome, SCID screening documented it as a symptom in CHARGE syndrome, Jacobsen syndrome, and trisomy 21, among others.
This list of disorders does not surprise Anne Comeau, PhD, Deputy Director of the New England Newborn Screening Program and Associate Professor of Pediatrics at the University of Massachusetts Medical School. Adding a new condition to a state newborn screening panel for a generally healthy population often “uncovers a spectrum of related disorders,” she says. Impaired T lymphocytes have been a known feature of the milder form of SCID called Omenn syndrome and in some children with trisomy 21, she points out, adding they haven't been well studied in other disorders. There are also children with low lymphocyte levels of no known cause who confound clinicians and researchers, says Dr. Puck. “We don't know the genes underlying their problems,” she points out. “Newborn screening identified these children, and now we must follow them to learn more about them.”
Another benefit of more states adopting SCID screening is data that may indicate a more accurate picture of the disorder's incidence. Because the disease is so rare and few states now screen for it, current incidence estimates probably aren't accurate, says Michele Caggana, ScD, Research Scientist at the New York State Department of Health's Wadsworth Center. Her experience in New York leads her to believe that it may be significantly more common than 1 in 50,000.
A New Paradigm
SCID screening is the first time many newborn screening programs are looking for molecular biomarkers, Caggana notes.
Implementation of SCID screening involves some challenges because testing DNA is new to many newborn screening labs, says Gary Hoffman, BS, Wisconsin State Laboratories' Director of Newborn Screening, who has provided assistance to other states implementing screening. Labs need expertise in DNA extraction, he notes, and specimen handling and quality assurance for SCID testing is more demanding than what is required for mass spectrometry. Dr. Comeau says that state labs experienced with molecular testing for infectious disease and bioterror agents can provide assistance. In fact, according to Hoffman, some states have their molecular labs handle SCID screening or have moved molecular lab staff into newborn screening labs.
States now have more help with SCID screening from the Centers for Disease Control and Prevention. It now includes SCID in its quality assurance program. The Newborn Screening Translational Research Network holds a monthly conference call about SCID screening, Dr. Caggana says.
Both actual screening for SCID and debate around the screening have raised awareness of the disease, but Dr. Caggana says it is still important to educate primary care physicians and other medical specialties about SCID. She recalls one New York physician who learned about SCID in grand rounds and then tested one of his pediatric intensive care unit (PICU) patients, who had the disorder. Babies with SCID may present in the PICU with sepsis or bad thrush, she says.
Dr. Caggana hopes that continued, widespread screening will help reveal additional genetic causes of SCID and help identify other immunodeficiencies with no previously known cause.