Incidence Of Severe Combined Immunodeficiency Research Articles

Delayed onset ADA-SCID presenting as secondary HLH in a patient with normal newborn screening

Severe combined immunodeficiency (SCID) is a rare genetic syndrome caused by aberrant immune cell development or function and is fatal without early identification and treatment. The Centers for Disease Control estimates the annual incidence of SCID to be one case per 40,000 to 100,000 live births. Newborn screening using T-cell receptor excision circles (TREC) allows for early detection and timely treatment of SCID. Adenosine deaminase (ADA) is a vital enzyme in the purine salvage pathway, and its deficiency results in disruption of T, B and NK cell development, accounting for 10–20% of SCID cases. The timing of ADA-SCID presentation ranges from birth to delayed onset disease. Importantly, without early recognition and treatment, delayed onset ADA-SCID results in accumulation of toxic metabolites causing immune dysfunction, recurrent infections, and subsequent organ damage. Recently, some groups have questioned whether traditional TREC newborn screening adequately identifies ADA-SCID, especially those cases with delayed onset. We present the case of a 2-year-old male with normal newborn screening but a history of recurrent otitis media and respiratory infections who developed multisystem organ failure and septicemia with Escherichia coli, candida, adenovirus and enterovirus despite broad-spectrum antimicrobials. The patient also had features of a hyperinflammatory syndrome with fever, pancytopenia, hypertriglyceridemia, and hyperferritinemia and was treated for hemophagocytic lymphohistiocytosis (HLH) with dexamethasone and plasma exchange followed by anakinra, etoposide, and emapalumab. The patient was maximally supported with mechanical ventilation, extracorporeal membrane oxygenation, and renal replacement therapy but had progressive clinical deterioration and ultimately expired. Autopsy was notable for thymic aplasia and erythrophagocytosis in the bone marrow and lymph nodes. Genetic testing revealed a heterozygous missense pathogenic variant in exon 7 in the ADA gene as well as novel heterozygous intronic variant of unknown significance in the ADA gene. Postmortem data suggests this patient had ADA-SCID with multi-pathogen infections and secondary HLH. This case potentially identifies a novel pathogenic variant in ADA missed by traditional TREC newborn screening and highlights the need to retain a high clinical suspicion of SCID in patients with a history of recurrent infections despite normal TREC screening.

Severe Combined Immunodeficiency (SCID) Screening in Arizona: Lessons Learned from the First 2 Years.

The incidence of severe combined immunodeficiency (SCID) in the USA was reported as 1 in 58,000 live births. In Arizona, it was anticipated that newborn screening would identify two to four cases of SCID per year. This estimate did not consider ethnic nuances in Arizona, with higher percentages of Native American and Hispanic populations compared to national percentages. The true incidence of SCID and non-SCID T cell lymphopenia has not previously been reported in Arizona. A retrospective chart review was performed on all abnormal SCID newborn screening (NBS) tests in Arizona from January 1, 2018, to December 31, 2019, using data from the Arizona Department of Health Services and the Phoenix Children's Hospital's electronic medical record [IRB# 20-025]. Seven infants were diagnosed with SCID, yielding an incidence of 1 in 22,819 live births. Four of these infants had Artemis-type SCID. Thirteen infants were identified with an abnormal initial NBS which ultimately did not lead to a diagnosis of SCID. Four of these infants were diagnosed with congenital syndromes associated with T cell lymphopenia. Infants of Hispanic ethnicity were over-represented in this cohort. Over 2years, NBS in Arizona confirmed an incidence more than 2.5 times that reported nationally. This increased incidence is likely reflective of Arizona's unique population profile, with a higher percentage of Native American population. The findings in our non-SCID cohort are in alignment with previously published data, except for an increased percentage of infants of Hispanic/Latino ethnicity, possibly reflecting Arizona's increased percentage of Hispanic/Latino population compared to the general US population.

Lessons Learned From Five Years of Newborn Screening for Severe Combined Immunodeficiency in Israel

Implementation of newborn screening (NBS) programs for severe combined immunodeficiency (SCID) have advanced the diagnosis and management of affected infants and undoubtedly improved their outcomes. Reporting long-term follow-up of such programs is of great importance. We report a 5-year summary of the NBS program for SCID in Israel. Immunologic and genetic assessments, clinical analyses, and outcome data from all infants who screened positive were evaluated and summarized. A total of 937,953 Guthrie cards were screened for SCID. A second Guthrie card was requested on 1,169 occasions (0.12%), which resulted in 142 referrals (0.015%) for further validation tests. Flow cytometry immune-phenotyping, T cell receptor excision circle measurement in peripheral blood, and expression of TCRVβ repertoire for the validation of positive cases revealed a specificity and sensitivity of 93.7% and 75.9%, respectively, in detecting true cases of SCID. Altogether, 32 SCID and 110 non-SCID newborns were diagnosed, making the incidence of SCID in Israel as high as 1:29,000 births. The most common genetic defects in this group were associated with mutations in DNA cross-link repair protein 1C and IL-7 receptor α (IL-7Rα) genes. No infant with SCID was missed during the study time. Twenty-two SCID patients underwent hematopoietic stem cell transplantation, which resulted in a 91% survival rate. Newborn screening for SCID should ultimately be applied globally, specifically to areas with high rates of consanguineous marriages. Accumulating data from follow-up studies on NBS for SCID will improve diagnosis and treatment and enrich our understanding of immune development in health and disease.

Ten Years of Newborn Screening for Severe Combined Immunodeficiency (SCID) in Massachusetts

To examine the outcomes of population newborn screening (NBS) for severe combined immunodeficiency (SCID) by using T-cell receptor excision circles (TRECs) after the first decade of implementation in Massachusetts.Infants born in Massachusetts screened through the New England Newborn Screening Program between February 1, 2009, and January 31, 2019.The authors present a population cohort of infants receiving NBS for SCID, both before and after mandatory NBS implementation in 2016.Of 720 038 infants screened, normal TRECs were identified in 99.71%. At least 1 abnormal specimen was identified in 2072 infants (0.29% of those screened). Of these infants, 1771 had an additional TREC result, which was normal, and were released from the screening program (83.8% of those with an abnormal TREC result before confirmatory flow cytometry and 1.7% after further lymphocyte phenotyping). Further evaluation by flow cytometry occurred in 237 infants (11.4% of those with at least 1 abnormal TREC result), and low naïve T-cell percentages were associated with a greater risk of a combined immunodeficiency. A total of 9 infants were diagnosed with SCID or leaky SCID, 7 were diagnosed with other combined immunodeficiencies, and 3 were diagnosed with athymia (0.4%, 0.3%, and 0.1%, respectively. of those with an abnormal TREC screen). The incidence of SCID or leaky SCID was reported as ∼1 in 80 000; however, more broadly, the incidence of severe T-cell lymphopenia for which definitive treatment was indicated was ∼1 in 50 000 infants. All patients with SCID or leaky SCID underwent hematopoietic cell transplant or gene therapy for which survival was 100%, and 1 patient with athymia underwent a successful thymus transplant. With NBS, the researchers successfully identified all known cases of SCID. Compared with survival before NBS by TREC, survival improved significantly for infants with SCID or leaky SCID (100% [n = 9] vs 57% [n = 7]. Of 162 infants with T-cell counts <2500 but above 1500 µL, no cases of SCID were identified, but 8 infants were diagnosed with partial DiGeorge syndrome.NBS of TREC levels is highly sensitive and specific, with the ability to improve early diagnosis of SCID. When compared with historical rates of SCID diagnosis and management before TREC evaluation by NBS, screening can reduce the time to transplant (3.4 months versus 6.5 months) and improve outcomes for infants with SCID.Screening for SCID has been a significant addition to NBS programs across the country, and multiple studies have suggested this to be a cost-effective strategy. As of December 2018, all 50 states have begun to screen for SCID at birth. SCID is often unrecognized in early life, but survival improves with early diagnosis. With this study, the authors provide long-term outcomes and highlight the benefit of these programs, suggesting a 43% reduction in mortality from a condition that can be successfully treated when identified early. From these data, the sensitivity, specificity, negative predictive value, and positive predictive value can be calculated (100%, 99.7%, 100%, and 0.91%, respectively). Notably, despite high sensitivity and specificity, a population prevalence of ∼1:50 000 to 80 000 lowers the positive predictive value of screening. Although early referral to an immunologist is important in infants with abnormal TREC results, these data also suggest the absolute risk of SCID in these infants is low (<1%). Thus, when counseling families of infants with an abnormal TREC screen, there is room for cautious optimism, pending results of definitive testing. More work is needed to better understand the short- and longer-term psychosocial impacts of a false-positive NBS result for SCID on families with unaffected infants after a positive screening test result.

First Year of TREC-Based National SCID Screening in Sweden.

Screening for severe combined immunodeficiency (SCID) was introduced into the Swedish newborn screening program in August 2019 and here we report the results of the first year. T cell receptor excision circles (TRECs), kappa-deleting element excision circles (KRECs), and actin beta (ACTB) levels were quantitated by multiplex qPCR from dried blood spots (DBS) of 115,786 newborns and children up to two years of age, as an approximation of the number of recently formed T and B cells and sample quality, respectively. Based on low TREC levels, 73 children were referred for clinical assessment which led to the diagnosis of T cell lymphopenia in 21 children. Of these, three were diagnosed with SCID. The screening performance for SCID as the outcome was sensitivity 100%, specificity 99.94%, positive predictive value (PPV) 4.11%, and negative predictive value (NPV) 100%. For the outcome T cell lymphopenia, PPV was 28.77%, and specificity was 99.95%. Based on the first year of screening, the incidence of SCID in the Swedish population was estimated to be 1:38,500 newborns.

Newborn Screening for Severe Combined Immunodeficiency: 10-Year Experience at a Single Referral Center (2009-2018).

In 2008, newborn screening (NBS) for severe combined immunodeficiency (SCID) began as a pilot study in Wisconsin and has recently been added to every state's newborn screen panel. The incidence of SCID is estimated at 1 per 58,000 births which may suggest infrequent NBS SCID screen positive results in states with low annual birth rates. In this study, we report our center's experience with NBS positive SCID screen referrals over a 10-year period. A total of 68 full-term newborns were referred to our center for confirmatory testing. Of these referrals, 50% were false positives, 12% were SCID diagnoses, 20% syndromic T cell lymphopenia (TCL) disorders, and 18% non-SCID, non-syndromic TCL. Through collaboration with our newborn screening lab, second-tier targeted gene sequencing was performed for newborns with SCID screen positive results from communities with known founder pathogenic variants and provided rapid genetic confirmation of SCID and non-SCID TCL disorders. Despite extensive genetic testing, two of the eight (25%) identified newborns with SCID diagnoses lacked a definable genetic defect. Additionally, our referrals included ten newborns who were otherwise healthy newborns with idiopathic TCL and varied CD3+ T cell number longitudinal trajectories. Collectively, referrals to our single site over a 10-year period describe a broad spectrum of medically actionable and idiopathic TCL disorders which highlight the importance of clinical immunology expertise in all states, demonstrate efficiencies and challenges for second-tier genetic testing, and further emphasize the need to development standardized evaluation algorithms for non-SCID TCL.

First Universal Newborn Screening Program for Severe Combined Immunodeficiency in Europe. Two-Years' Experience in Catalonia (Spain).

Severe combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TRECs) in dried blood spot (DBS) samples. Early detection of this condition speeds up the establishment of appropriate treatment and increases the patient's life expectancy. Newborn screening for SCID started in January 2017 in Catalonia, the first Spanish and European region to universally include this testing. The results obtained in the first 2 years of experience are evaluated here. All babies born between January 2017 and December 2018 were screened. TREC quantification in DBS (1.5 mm diameter) was performed with the Enlite Neonatal TREC kit from PerkinElmer (Turku, Finland). In 2018, the retest cutoff in the detection algorithm was updated based on the experience gained in the first year, and changed from 34 to 24 copies/μL. This decreased the retest rate from 3.34 to 1.4% (global retest rate, 2.4%), with a requested second sample rate of 0.23% and a positive detection rate of 0.02%. Lymphocyte phenotype (T, B, NK populations), expression of CD45RA/RO isoforms, percentage and intensity of TCR αβ and TCR γδ, presence of HLA-DR+ T lymphocytes, and in vitro lymphocyte proliferation were studied in all patients by flow cytometry. Of 130,903 newborns screened, 30 tested positive, 15 of which were male. During the study period, one patient was diagnosed with SCID: incidence, 1 in 130,903 births in Catalonia. Thirteen patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 10,069 newborns (43% of positive detections). Nine patients were considered false-positive cases because of an initially normal lymphocyte count with normalization of TRECs between 3 and 6 months of life, four infants had transient lymphopenia due to an initially low lymphocyte count with recovery in the following months, and three patients are still under study. The results obtained provide further evidence of the benefits of including this disease in newborn screening programs. Longer follow-up is needed to define the exact incidence of SCID in Catalonia.

A Cost-Effectiveness Analysis of Newborn Screening for Severe Combined Immunodeficiency in the UK.

Severe combined immunodeficiency (SCID) can be detected through newborn bloodspot screening. In the UK, the National Screening Committee (NSC) requires screening programmes to be cost-effective at standard UK thresholds. To assess the cost-effectiveness of SCID screening for the NSC, a decision-tree model with lifetable estimates of outcomes was built. Model structure and parameterisation were informed by systematic review and expert clinical judgment. A public service perspective was used and lifetime costs and quality-adjusted life years (QALYs) were discounted at 3.5%. Probabilistic, one-way sensitivity analyses and an exploratory disbenefit analysis for the identification of non-SCID patients were conducted. Screening for SCID was estimated to result in an incremental cost-effectiveness ratio (ICER) of £18,222 with a reduction in SCID mortality from 8.1 (5–12) to 1.7 (0.6–4.0) cases per year of screening. Results were sensitive to a number of parameters, including the cost of the screening test, the incidence of SCID and the disbenefit to the healthy at birth and false-positive cases. Screening for SCID is likely to be cost-effective at £20,000 per QALY, key uncertainties relate to the impact on false positives and the impact on the identification of children with non-SCID T Cell lymphopenia.

Cost-effectiveness of newborn screening for severe combined immunodeficiency.

Severe combined immunodeficiency (SCID) is a condition that often results in severe infections and death at young age. Early detection shortly after birth, followed by treatment before infections occur, largely increases the chances of survival. As the incidence of SCID is low, assessing cost-effectiveness of adding screening for SCID to the newborn screening program is relevant for decision making. Lifetime costs and effects of newborn screening for SCID were compared to a situation without screening in the Netherlands in a decision analysis model. Model parameters were based on literature and expert opinions. Sensitivity analyses were performed. Due to earlier detection, the number of deaths due to SCID per 100,000 children was assessed to decrease from 0.57 to 0.23 and a number of 11.7 quality adjusted life-years (QALYs) gained was expected. Total yearly healthcare costs, including costs of screening, diagnostics, and treatment, were €390,800 higher in a situation with screening compared to a situation without screening, resulting in a cost-utility ratio of €33,400 per QALY gained.Conclusion: Newborn screening for SCID might be cost-effective. However, there is still a lot of uncertainty around the cost-effectiveness estimate. Pilot screening projects are warranted to obtain more accurate estimates for the European situation. What is Known: • Severe combined immunodeficiency (SCID) is a condition that often results in severe infections and death at a young age. • As the incidence of SCID is low, assessing cost-effectiveness of adding screening for SCID to the newborn screening program is needed. What is New: • Newborn screening for SCID is expected to reduce mortality from 0.57 to 0.23 per 100,000 children at additional healthcare costs of €390,800. The cost-utility ratio is €33,400 per QALY gained. • Due to large uncertainty around cost-effectiveness estimates, pilot screening projects are warranted for Europe.

The Cost-Effectiveness Of Screening For Severe Combined Immunodeficiency (SCID) In The UK NHS Newborn Bloodspot Screening Programme

To assess the cost-effectiveness of including screening for severe combined immunodeficiency (SCID) in the NHS newborn bloodspot screening programme. A decision tree model with life-table estimates of outcomes was built. Model structure and parameterisation were informed by systematic review and expert clinical judgment. A public service perspective was used and lifetime costs and quality adjusted life years (QALYs) were discounted at 3.5%. Standard treatment following screening was hematopoietic stem cell transplantation with additional treatment options for adenosine deaminase deficiency SCID. The model estimated the number of non-SCID cases identified incidentally. Probabilistic sensitivity analyses was undertaken. An exploratory disbenefit analysis was conducted for false positives and those diagnosed with non-SCID T-cell lymphopenia (TCL) who would have presented as healthy at birth. Screening for SCID was estimated to result in 310 (72-811) presumptive positive cases per year including 260 (25-760) false positives cases, 7 (1-21) preterm cases, 26 (9-50) non-SCID TCL cases and 17 (14-22) SCID cases. Screening would increase overall QALYs and costs and result in an incremental cost-effectiveness ratio (ICER) of £17,642. The increase in QALYs was driven by improved survival in the screened cohort with mortality reducing from 8 (5.3-12) deaths to 1.7 (0.6-4.1). Results were sensitive to a number of parameters including the cost of the screening test, the incidence of SCID and quality of life estimates. The disbenefit analysis estimated that to push the cost-effectiveness over the £20,000 threshold the 6.5 (1.5-16) healthy at birth cases would need to experience a disbenefit of 2 QALYs and the false positive cases a disbenefit of over 12 quality adjusted days. Screening for SCID is potentially cost-effective at £20,000 per QALY, key uncertainties relate to the impact of false positives and the identification of children with non-SCID TCL.

Neurologic event-free survival demonstrates a benefit for SCID patients diagnosed by newborn screening.

TO THE EDITOR: Severe combined immunodeficiency (SCID) may be diagnosed via newborn screening (NBS) by measuring T-cell receptor excision circles.[1][1],[2][2] The incidence of SCID has risen, and this is rise attributed to the identification of patients who would have previously died of infections

Newborn Screening for Severe Combined Immunodeficiency in Israel

Newborn screening (NBS) programs for severe combined immunodeficiency (SCID), the most severe type of primary immunodeficiency, are being implemented in more and more countries with every passing year. Since October 2015, SCID screening via T cell receptor excision circle (TREC) quantification in dried blood spots (DBS) has been part of the Israeli NBS program. As an NBS program in its infancy, SCID screening is still evolving, making gathering input from the various programs crucial for compiling an ideal screening algorithm. The relatively high rate of consanguineous marriages in Israel, especially among non-Jews, correlates with an increased incidence of SCID. The Israeli algorithm uses a commercial kit and consists of a two-Guthrie card confirmation system prior to referral to a national immunology center. Preliminary data from the first year and a half of SCID screening in Israel has identified a surprisingly high prevalence of DNA cross-link repair protein 1c (DCLRE1C; ARTEMIS) mutations as the cause of SCID in Israel. The clinically unbiased nature of SCID screening helps unearth mild/leaky SCID phenotypes, resulting in a better understanding of true SCID prevalence and etiology.

Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

A Kwan, RS Abraham, R Currier. JAMA. 2014;312(7):729–738 To assess the results of a spectrum of state-based newborn screening programs using the T-cell receptor excision (TREC) testing approach to develop more accurate population-based incidence of severe combined immunodeficiency (SCID) and other conditions associated with T-cell lymphopenia and document the effectiveness of early intervention in those newborns found to have a significant immunologic abnormality. Cumulative TREC newborn screening data were evaluated from 10 states plus the Navajo Nation involving ∼3 million newborns. This was an epidemiologic and retrospective observational study based on states invited to submit SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. The data evaluated were collected from January 2008 through …

Newborn Screening for Severe Combined Immunodeficiency

Newborn screening (NBS) for severe combined immunodeficiency (SCID) utilizing the T-cell receptor excision circle assay is a sensitive and specific method to detect T-cell lymphopenia in early infancy. Starting in 2008, several programs have implemented SCID NBS with successful detection of SCID-affected infants; currently over two thirds of U.S. infants receive SCID NBS. Population-based, unbiased screening has established an incidence of SCID to be 1 in 58,000 births, and has revealed a distribution of SCID genotypes different from prior reports from specific SCID treatment centers. Detecting SCID-affected infants in the newborn period allows for timely implementation of protective measures and optimal definitive treatment prior to the onset of life-threatening infections. Infants with non-SCID T-cell lymphopenia also detected by NBS may have one of several recognized syndromes in which lymphocyte development may be impaired, as well as other conditions associated with secondary T-cell lymphopenia.

Higher prevalence of immune deficiency syndrome found in infants: study finds nearly twice as many newborns affected by severe combined immunodeficiency than previous research had estimated.

Higher prevalence of immune deficiency syndrome found in infants: study finds nearly twice as many newborns affected by severe combined immunodeficiency than previous research had estimated.

Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States.

Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births. To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. Epidemiological and retrospective observational study. Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test. Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. Newborn screening in 11 programs in the United States identified SCID in 1 in 58,000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

An analysis and decision tool to measure cost benefit of newborn screening for severe combined immunodeficiency (SCID) and related T-cell lymphopenia

Severe combined immunodeficiency (SCID) is a group of syndromes resulting from genetic defects causing absence in T-cell and B-cell function, leading to serious and life-threatening infections. SCID is often fatal in the first 2years of life if not identified and properly treated. While additional laboratory methods are being developed, the current T-cell receptor excision circle assay has proven to have outstanding specificity and sensitivity to accurately identify infants with SCID and other T-cell lymphopenia. The Jeffrey Modell Foundation (JMF) has a long history of advocacy and continues to promote newborn screening for SCID to be implemented in the United States and worldwide. Based on reports provided by California, New York, Texas, and Wisconsin on the results of their population based newborn screening programs, the overall incidence of SCID averaged 1:33,000 and T-cell lymphopenia averaged 1:6,600. JMF has developed a working algorithm or "decision tree", validated by peer-reviewed scientific literature, to be used by Public Health Departments and Health Ministries in states, countries, and regions throughout the world. This decision tool allows for local or regional data to be applied to measure the threshold and economic impact of implementing newborn screening for SCID and T-cell lymphopenia.

Autoimmunity due to RAG deficiency and estimated disease incidence in RAG1/2 mutations

Autoimmunity due to RAG deficiency and estimated disease incidence in RAG1/2 mutations

Severe Combined Immunodeficiency (SCID) in Canadian Children: A National Surveillance Study

PurposeSevere Combined Immune Deficiency (SCID) is universally fatal unless treated with hematopoietic stem cell transplantation (HSCT). Following the identification of disseminated Bacille Calmette-Guérin (BCG) infections in Canadian First Nations, Métis and Inuit (FNMI) children with unrecognized primary immune deficiencies, a national surveillance study was initiated in order to determine the incidence, diagnosis, treatment and outcome of children with SCID in Canada.MethodsCanadian pediatricians were asked to complete a monthly reporting form if they had seen a suspected SCID case, from 2004 to 2010, through the Canadian Paediatric Surveillance Program (CPSP). If the case met CPSP SCID criteria, more detailed data, including demographics and clinical information about investigations, treatment and outcome was collected.ResultsA total of 40 cases of SCID were confirmed for an estimated incidence of SCID in non-FNMI Canadian children of 1.4 per 100,000 live births (95 % CI 1 to 1.9/100,000). The proportion of SCID cases that were FNMI (17.5 %) was almost three times higher than was expected on the basis of proportion of the pediatric population estimated to be FNMI (6.3 %) resulting in an estimated incidence of 4.4 per 100,000 live births (95 % CI 2.1 to 9.2/100,000) in FNMI Canadian children. The mean age at diagnosis for all SCID cases was 4.2 months (range 1–583 days). There were 12 deaths (30 %; 95 % CI 18–46 %); seven died of confirmed or suspected infections before they could receive an HSCT.ConclusionsThe frequency of SCID cases in FNMI children is higher than in the general Canadian pediatric population. The high mortality rate, due primarily to infection, suggests that early diagnosis by newborn screening followed by HSCT could significantly benefit children with SCID.

Incidence of severe combined immunodeficiency through newborn screening in a Chinese population.

In order to know the true incidence of severe combined immunodeficiency (SCID) in a Chinese population, we conducted and implemented SCID newborn screening in Taiwan. Between May 1, 2010 and December 31, 2011, the National Taiwan University Hospital Newborn Screening Center screened all newborns for T-cell lymphopenia by measuring the copy number of T-cell receptor excision circles (TRECs) and RNase P. Newborns with low TREC values were subjected to complete blood cell counts and flow cytometry. A total of 106,391 newborns were screened using the TREC assay over a period of 19 months. Five newborns were immediately referred for confirmatory tests, including two SCID patients and two patients with persistent T-cell lymphopenia; a third SCID patient was found 2 months after the study period. All three SCID cases received stem cell transplantation at the age of 2-5 months. We also identified five cases of 22q11.2 microdeletion syndrome. During this period, two SCID patients from among the unscreened newborns were reported, and they died at ages 3 months and 4 months, respectively. Newborn screening to measure the number of TREC copies successfully identifies newborns with T-cell lymphopenia, 22q11.2 microdeletion syndrome, and other high-risk conditions. Taken together, the incidence of T-cell lymphopenia in apparently healthy newborns is more than 1 in 11,821, and further attention to their immune functions is warranted.