Credit: Vera Kratochvil
Severe combined immunodeficiency (SCID) may be nearly twice as common as we thought, new research suggests.
The study is the first combined analysis of more than 3 million infants screened for SCID in 10 US states and the Navajo Nation.
The results suggest SCID may affect as many as 1 in 58,000 infants. Previous estimates had indicated that 1 in 100,000 infants may be born with SCID.
This study and a related editorial were published in JAMA.
Jennifer Puck, MD, of the University of California, San Francisco, and her colleagues analyzed infants from 10 states and the Navajo Nation who were born from January 2008 through July 2013 and were screened for SCID.
The screening detected 52 cases of SCID among the 3,030,083 newborns, suggesting the disorder may affect roughly 1 in 58,000 infants.
The incidence of SCID was not significantly different in any state program, but it was higher in the Navajo Nation, where an ancestral trait is known to confer a higher risk of the disease.
Of the 52 infants who had SCID, 49 received therapies such as hematopoietic stem cell transplants, enzyme replacement therapy, and/or gene therapy. Three infants died before receiving treatment, and 4 children died after transplant, but the other 45 treated infants survived.
Of those 52 cases of SCID identified by newborn screening, 9 were considered “leaky SCID.” These infants had an incomplete mutation in a typical SCID gene, retaining small amounts of immune function that can actually be detrimental because the poorly regulated cells can attack the child’s own tissues.
“We’re finding that leaky SCID is more common than previously thought,” Dr Puck said. “Before screening, we’d typically not make the diagnosis for several months or even years, but because of newborn screening, they are being treated before they get into any trouble.”
The screening test detects more than a dozen genetic causes of SCID, in addition to other conditions with significantly low T cells. The researchers discovered that population-based testing uncovers a broader range of the underlying genetic causes for SCID than previously known.
For example, X-linked SCID, a form of the disorder caused by mutations in a gene on the X chromosome and affecting only males, was previously thought to account for half of SCID cases. But this study showed that only 19% of SCID infants had X-linked disease with a corresponding increase in other gene defects.
Moreover, the proportion of SCID infants without a known genetic defect (15%) was higher than anticipated, indicating that widespread screening presents opportunities to discover previously unknown genes implicated in SCID.
“The whole point of newborn screening is to identify conditions that are treatable, and for which early treatment saves lives,” Dr Puck said. “The excellent outcomes of SCID infants across the country reported in this study prove that SCID is such a condition.”
