Idiopathic T cell lymphopenia identified in New York State Newborn Screening

Albin-Leeds, Stephanie; Ochoa, Juliana Lucía; Mehta, Harshna; Vogel, Beth; Casini, Michèle; Bonagura, Vincent R.; Lehman, Heather K.; Ballow, Mark; Rubinstein, Arye; Siegel, Subhadra; Weiner, Leonard B.; Weinberg, Geoffrey A.; Cunningham‐Rundles, Charlotte

doi:10.1016/j.clim.2017.07.002

Cited by 28 publications

(12 citation statements)

References 17 publications

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“…Many of them recover spontaneously ( 11 ). A recent study by Albin-Leeds et al ( 29 ) has reported that while additional infants with T cell lymphopenia are identified in NBS panels, they seem to do well clinically. Children with severe genetic syndromes often present other, more urgent symptoms at birth.…”

Section: Discussionmentioning

confidence: 99%

First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency—Clinical Achievements and Insights

et al. 2017

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Severe combined immunodeficiency (SCID), the most severe form of T cell immunodeficiency, is detectable through quantification of T cell receptor excision circles (TRECs) in dried blood spots obtained at birth. Herein, we describe the results of the first year of the Israeli SCID newborn screening (NBS) program. This important, life-saving screening test is available at no cost for every newborn in Israel. Eight SCID patients were diagnosed through the NBS program in its first year, revealing an incidence of 1:22,500 births in the Israeli population. Consanguine marriages and Muslim ethnic origin were found to be a risk factor in affected newborns, and a founder effect was detected for both IL7Rα and DCLRE1C deficiency SCID. Lymphocyte subset analysis and TREC quantification in the peripheral blood appear to be sufficient for confirmation of typical and leaky SCID and ruling out false positive (FP) results. Detection of secondary targets (infants with non-SCID lymphopenia) did not significantly affect the management or outcomes of these infants in our cohort. In the general, non-immunodeficient population, TREC rises along with gestational age and birth weight, and is significantly higher in females and the firstborn of twin pairs. Low TREC correlates with both gestational age and birth weight in extremely premature newborns. Additionally, the rate of TREC increase per week consistently accelerates with gestational age. Together, these findings mandate a lower cutoff or a more lenient screening algorithm for extremely premature infants, in order to reduce the high rate of FPs within this group. A significant surge in TREC values was observed between 28 and 30 weeks of gestation, where median TREC copy numbers rise by 50% over 2 weeks. These findings suggest a maturational step in T cell development around week 29 gestation, and imply moderate to late preterms should be screened with the same cutoff as term infants. The SCID NBS program is still in its infancy, but is already bearing fruit in the early detection and improved outcomes of children with SCID in Israel and other countries.

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Section: Discussionmentioning

confidence: 99%

First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency—Clinical Achievements and Insights

et al. 2017

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“…2,13,14 TRECs count reflects T cell levels and significant benefits have been gained in the diagnosis of SCID by introduction of TRECs in SCID screening programs with high sensitivity and specificity. [15][16][17] Preliminary data from U.S. screening program suggest that 1 of 30,000 to 50,000 infant can have SCID. Our country and such countries with a high rate of consanguineous marriage (Saudi Arabia and Kuwait) data revealed higher numbers than United States.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Lymphopenia Screening Is Important for Early Diagnosis of Severe Combined Immunodeficiency

et al. 2021

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Objective T-cell receptor excision circles are expensive for neonatal severe combined immunodeficiency screening in developing countries. We aimed to detect immunodeficiencies presenting with lymphopenia to enable screening in the general population and to improve awareness regarding lymphopenia among clinicians. Study Design This study was conducted prospectively. In all newborns included, complete blood count from umbilical cord blood samples was recorded. Absolute lymphopenia was defined as absolute lymphocyte count <3,000/mm3 in umbilical cord blood sample. Complete blood count was repeated at month 1 in cases found to have lymphopenia. Results Overall, 2,000 newborns were included in the study. Absolute lymphopenia was detected in 42 newborns (2.1%), while lymphocyte count was >3,000/mm3 in 1,958 newborns (97.9%). Two infants with persisted lymphopenia at the end of the first month; therefore, further evaluations such as lymphocyte subsets for severe combined immunodeficiency (SCID) were done. In the first infant, the lymphocyte subgroups were detected as compatible with T (−), B (−), natural killer cells (NK) (+) SCID phenotype RAG defect. Sanger sequencing revealed that NM_000448 c.2209C > T (p.R737C) homozygous mutation of RAG1 gene. In the other infant, the lymphocyte subgroups were found as considered with T (−), B (+) NK (−) SCID phenotype JAK3 defect. Both patients underwent hematopoietic stem cell transplantation from human leukocyte antigen-matched family member. Conclusion Absolute lymphopenia by complete blood count is a more simpler, relatively noninvasive and inexpensive screening methodfor detection of SCID in newborns compared with T-cell receptor excision circles technique. Key Points

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“…There are several possible outcomes of patients with ITL. First, the T cell counts may normalize over time, but in our and others experience, the timing of this can vary greatly and may take up to 9 months ( 9 , 20 ). In other cases, the T cell counts may be persistently low and decrease over time, which would necessitate consideration of proceeding to HSCT ( 9 , 20 ).…”

Section: Idiopathic Tcl—a Unique Management Problem For Nbsmentioning

confidence: 98%

“…A number of infants who failed the NBS for SCID are diagnosed with idiopathic T cell lymphopenia (ITL) ( 1 , 9 , 20 ). These patients have low T cell numbers, but not low enough to be considered SCID (>300 autologous T cells/mm 3 ), and lack a genetic diagnosis that results in SCID or a known cause of TCL.…”

Section: Idiopathic Tcl—a Unique Management Problem For Nbsmentioning

confidence: 99%

A Practical Approach to Newborn Screening for Severe Combined Immunodeficiency Using the T Cell Receptor Excision Circle Assay

et al. 2017

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Severe combined immunodeficiency (SCID) is a life-threatening condition of newborns and infants caused by defects in genes involved in T cell development. Newborn screening (NBS) for SCID using the T cell receptor excision circle (TREC) assay began in Wisconsin in 2008 and has been adopted or is being implemented by all states in 2017. It has been established that NBS using the TREC assay is extremely sensitive to detect SCID in the newborn period. Some controversies remain regarding how screening positives are handled by individual states, including when to perform confirmatory flow cytometry, what is the necessary diagnostic workup of patients, what infection prophylaxis measures should be taken, and when hematopoietic stem cell transplantation should occur. In addition, the TREC can also assay detect infants with T cell lymphopenia who are not severe enough to be considered SCID; management of these infants is also evolving.

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Idiopathic T cell lymphopenia identified in New York State Newborn Screening

Cited by 28 publications

References 17 publications

First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency—Clinical Achievements and Insights

First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency—Clinical Achievements and Insights

Neonatal Lymphopenia Screening Is Important for Early Diagnosis of Severe Combined Immunodeficiency

A Practical Approach to Newborn Screening for Severe Combined Immunodeficiency Using the T Cell Receptor Excision Circle Assay

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