Newborn Screening for SCID in New York State: Experience from the First Two Years

Abstract

Purpose To describe the process and assess outcomes for the first 2 years of newborn screening for severe combined immunodeficiency (SCID NBS) in New York State (NYS). Methods The NYS algorithm utilizes a first-tier molecular screen for TRECs (T-cell receptor excision circles), the absence of which is indicative of increased risk of immunodeficiency. Results During the first 2 years, 485,912 infants were screened for SCID. Repeat specimens were requested from 561 premature and 746 non-premature infants with low or borderline TRECs. A total of 531 infants were referred for diagnostic evaluation leading to identification of 10 infants with SCID and 87 with a clinically significant non-SCID abnormality based on flow cytometry or CBC results (positive predictive value 20.3 %). Nine infants were diagnosed with typical SCID and one with leaky SCID. SCID diagnoses included two patients with adenosine deaminase deficiency, three patients with typical and one with leaky IL2RG-related SCID, one patient with IL7Rα-related SCID, and three cases of typical SCID, etiology unknown. TRECs were undetectable in eight of the nine babies with typical SCID. Infants with other non-SCID conditions included 27 patients with a syndrome that included T-cell impairment, 18 of which had DiGeorge syndrome. Seventeen infants had T-cell impairment secondary to another clinically significant condition, and 13 were classified as ‘other’. Among 30 infants classified as idiopathic T-cell lymphopenia, 11 have since resolved, and the remainder continues to be followed. One infant with undetectable TRECs had normal follow-up studies. Molecular studies revealed the presence of two changes in the infant’s DNA. Conclusions Overall, ten infants with SCID were identified during the first 2 years of screening in NYS, yielding an incidence of approximately 1 in 48,500 live births, which is consistent with the incidence observed by other states screening for SCID. The incidence of any clinically significant laboratory abnormality was approximately 1 in 5,000; both estimates are higher than estimates prior to the onset of newborn screening for SCID. Improvements to the NYS algorithm included the addition of a borderline category that reduced the proportion of infants referred for flow cytometric analysis, without decreasing sensitivity. We identified a large number of infants with abnormal TRECs and subsequent idiopathic T-cell lymphopenia. Long-term follow-up studies are needed to determine the prognosis and optimal treatment for this group of patients, some of whom may present with previously unrecognized, transient lymphopenia of infancy.

Newborn Blood Spot Screening Test Using Multiplexed Real-Time PCR to Simultaneously Screen for Spinal Muscular Atrophy and Severe Combined Immunodeficiency

“…All samples showed the typical amplification curves expected for TREC, SMN1, and RPP30. TREC Cq values obtained by the in situ DBS triplex assay showed a slight decrease (mean 0.4 Cq) compared to those from the duplex assay but were consistent with the overall ranges for term newborns reported by public health newborn screening programs (11)(12)(13)(14). The Cq values for SMN1 showed a near-gaussian distribution (Fig.…”

“…SCID is the first NBS condition for which DNA analysis is the primary (first-tier) screening method. Since the initial pilot experiences in 2 US state public health laboratories (11,12 ), SCID-NBS has expanded to many other state programs (13,14 ) and now covers the majority of newborns in the US as well as many newborns globally (15 ). SCID-NBS prevents infant death through early medical intervention and is highly cost-effective (16,17 ).…”

Determination of Reference Values for Trec and Krec in Dry Blood Spots of Newborns From Different Gestation Ages in Sverdlovsk Region

“…Более высокая частота аномальных результа-тов количества TREC у недоношенных новорож-денных отмечается во многих исследованиях [16,20,32,48]. В этом контексте незрелость иммун-ной системы как фактор, имеющий временный эффект, обусловленный гестационным возрас-том, трудно отделим от специфических факторов, связанных с состоянием здоровья недоношенных новорожденных.…”

Tandem mass spectrometric determination of purine metabolites and adenosine deaminase activity for newborn screening of ADA–SCID

“…Since 2008, a growing number of newborn screening programs have successfully implemented populationbased screening for SCID (Puck 2011;Verbsky et al 2012;Kwan et al 2013;Vogel et al 2014). The addition of this disorder as a primary target at Newborn Screening Ontario was recently approved by the Ministry of Health and Long Term Care, making Ontario the first Canadian province to offer this test.…”