Newborn Screeningand SevereCombined ImmuneDeficiency

Dr. Allen Cherer

April (April 22-29) has been designated asNational Primary ImmunodeficiencyAwareness Month and provides anopportunity to better understand the morethan 250 rare, genetic disorders in whichthe body’s normal immune system isabsent or functions improperly. Since animportant function of the immune systemis to protect against infection, patientswith primary immune deficiency have anincreased susceptibility to infection.

Severe Combined Immune Deficiency(SCID), popularized in the 1976 movie“The Boy in the Plastic Bubble”, isgenerally considered to be the mostserious of the primaryimmunodeficiencies.

There are at least 13 different geneticdefects that can cause the disease; allof which are present at birth, involvemissing T lymphocytes which areimportant in identifying and attackingperceived “invaders”, and affect thefunction of B lymphocytes whichproduce antibodies against infection.

The absence of T lymphocytes andantibody immunity results in severeinfections, diarrhea, and failure tothrive. Regardless of the genetics,patients invariably succumb to an earlydeath due to overwhelming infection.New approaches to diagnosis andmanagement have changed what atone time was a dismal prognosis.

Treatment options have come a longway over the past 4 decades and includeenzyme replacement, bone marrowtransplant, and gene therapy. Paramountto this change is early diagnosis beforethe infant has had a chance to developany serious infections.

The most effective therapy to date isimmune reconstitution via stem celltransplant which has been shown to behighly successful (94%) if performed by3.5 months of age. Hence, timing iscrucial in terms of diagnosis andtreatment.

Typically, infants with SCID appeartotally normal at birth and have nofamily history of immunodeficiency. Inthe past, patients were primarilyidentified either by previous familyhistory, physical manifestations, orafter onset of life-threateninginfection.

Early identification of SCID has beenachieved through the use of the 7-cellreceptor excision circle (TREC) assayas part of the routine newbornscreening program.

Absent or low TREC levels can indicateinsufficient T lymphocyte productioncharacteristic of SCID, as well as low Tlymphocyte, non-SCID conditions asseen in DiGeorge Syndrome, Trisomy21, CHARGE Syndrome, and ataxiatelangiectasia. On May 21, 2010, TheU.S. Department of Health and HumanServices (HHS) recommended thatevery state include the assay as part ofthe newborn screen.

In the landmark study based onretrospective data on more than 3million infants from 11 newbornscreening programs using the TRECmethodology conducted by JenniferPuck, MD and colleagues andpublished August 20, 2014 in TheJournal of the American MedicalAssociation, the value of earlydetection and treatment of SCID wasconfirmed.

In addition, the study found anincidence rate almost twice as great (1in 58,000 births) as had been previouslyestimated. Since the point of newbornscreening is to identify conditions forwhich early treatment is life-saving, thestudy was a crucial step in theadoption of universal screening.

As of April 1, 2016, all, except for 11,states have adopted routine newbornscreening programs for SCID. A 2016study published in the Journal ofPediatrics by Ding and others providedan eloquent cost-benefit analysis ofnewborn screening in the treatment ofSevere Combined Immune Deficiency.

Based on data obtained from 86,000infants in Washington state, the studyshowed that newborn screening forSCID is clearly cost-effective. Hopefully,the study provides additional support ineconomic terms for the adoption ofuniversal screening programs in all 50states.