Science + Technology

Two New UCLA Studies Show Benefits of Newborn Screening for ‘Bubble Boy Disease’


Two new UCLA studies show that newborn screening for SevereCombined Immunodeficiency (SCID) — a rare, treatable disorder of the immunesystem commonly known as "bubble boy disease" — is both cost-effective andcould be done accurately using a two‑tiered testing method.

"We wanted to determine whether testing for SCID should beadded to the universal screening panel for genetic disorders," said Dr. SeanMcGhee, clinical instructor of pediatric immunology at Mattel Children'sHospital at UCLA. "Treatment is now advanced enough that 95 percent ofchildren can be cured, but newborns must be detected in the first month, beforethe onset of severe infections."

In the first study — detailed in the November edition of theJournal of Pediatrics — UCLA researchers concluded that SCID screening couldresult in a large benefit to infants, making screening relativelycost-effective in spite of the low incidence of the disease. However, anadequate test would be critical to cost-effectiveness.

The analysis is the first of its kind to examine formallycost and benefits of SCID newborn screening.

To conduct the study, researchers used information about thecosts of diagnosing and treating SCID and the benefits of early diagnosis, andperformed a cost-benefit analysis comparing universal screening with screeningonly those with a family history of SCID.

Researchers determined that a SCID screening test that costless than five dollars with a false-negative rate of 0.9 percent and afalse-positive rate of 0.4 percent would be considered cost-effective bymost currently accepted standards.

A nationwide screening program would cost an additional$23.9 million per year for screening costs, but would result in 760 yearsof life saved per year of screening.

In a related pilot study — described in the December editionof Molecular Genetics and Metabolism — McGhee and his colleagues looked atusing a "two-tiered" strategy to improve the accuracy of SCID screenings.

"Existing tests for SCID are pretty good by themselves, butthey do not provide sufficient accuracy in diagnosing the disorder to make themcost-effective," McGhee said. "We wanted to see if combining the two testswould limit the false positive results."

The current basis for the screening test is measurement ofthe number of lymphocytes at the time of birth that are normally very high, butvery low in SCID infants. The screening is done by using dried blood samplesobtained for other newborn screenings.

In the retrospective analysis, investigators measured serumor plasma levels of interleukin-7 (IL-7), a T-cell growth cytokine elevated inSCID, in combination with the previously developed T-cell receptorrecombination excision circles assay.

They found that combining the tests in a two-tiered strategydecreased the false positive rate to nearly zero, which would be sufficient toallow cost-effective screening.

McGhee added that this strategy should be addressed in amulti-center, prospective trial to determine accurately the incidence,specificity, sensitivity and cost of SCID newborn screening.

The incidence of SCID is unknown but may be more common thanpublished estimates because infants frequently die of infection beforediagnosis. If an infant is diagnosed — preferably within the first month oflife — and before their first infection, most can be treated with a bone-marrowtransplant. About half of the patients can be cured; the other half may requireintravenous immune globulin therapy treatments, but can live normal lives.

Other UCLA authors on both studies included Dr. E. Richard Stiehm and Dr. Edward McCabe. In addition, Dr. MortonCowan, University of California, San Francisco, and Dr. Paul Krogstad,UCLA, co-authored the study on the two-tiered universal newborn screeningstrategy.

Support for all research was provided by the human andmolecular development training grant at the David Geffen School of Medicine atUCLA, NIH/NICHD and the Culpepper Biomedical Pilot Initiative of the John D.Rockefeller Foundation.

McCabe is an adviser to GeneFluidics,a nanotechnology company involved in genetic testing.



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