Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency

Marca, Giancarlo la; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Duse, Marzia; Malvagia, Sabrina; Lippi, Francesca; Funghini, Silvia; Bianchi, Leila; Bona, Maria Luisa Della; Valleriani, Claudia; Ombrone, Daniela; Moriondo, Maria; Villanelli, Fabio; Speckmann, Carsten; Adams, Stuart; Gaspar, Bobby; Hershfield, Michael S.; Santistéban, Inés; Fairbanks, Lynette D.; Ragusa, Giovanni; Resti, Massimo; Martino, Maurizio de; Guerrini, Renzo; Azzari, Chiara

doi:10.1016/j.jaci.2012.08.054

Cited by 60 publications

(42 citation statements)

References 23 publications

(35 reference statements)

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“…Up to now no later onset ADA-SCID patients have been identified at birth, so no data are present in literature on the natural history of a later phenotype [23]. The present method offers, for the first time, the possibility to get the diagnosis of ADA-SCID at birth, before onset of infectious disease.…”

Section: Discussionmentioning

confidence: 97%

“…ADA enzymatic activity, immunoglobulin levels, lymphocyte subsets and proliferation as well as ADA gene sequence were performed. Data obtained from all the biochemical and molecular analysis let to include our first patient as possible late onset ADA-SCID [23].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, delayed ADA-SCID false negative cases by TREC test have been recently described [23][24][25] Within the last 7 years (2004-2011) approximately 250,000 births occurred in Tuscany, among them four ADA-SCID patients were diagnosed. These preliminary data show the incidence in our catchment area seems to be greater than about 1:500,000 as reported in literature [26].…”

Section: Discussionmentioning

confidence: 99%

“…Three were born in Tuscany before ADA-SCID was included in the newborn screening panel and six were from other screening laboratories. Clinical and genetics details on ADA-SCID patients and the correlation of enzyme residual activity and metabolite' levels have been described by la Marca et al [23].…”

Section: Patientsmentioning

confidence: 99%

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The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry

Marca

Giocaliere

Malvagia

et al. 2014

Journal of Pharmaceutical and Biomedical Analysis

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a b s t r a c tSevere combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early. The aim of this study was to set-up a robust method suitable for screening with a minimized preparation process and with inexpensive running costs, for diagnosing ADA-SCID by tandem mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn screening program.We describe a protocol revised to incorporate adenosine and 2-deoxyadenosine testing into an expanded newborn screening program. We assessed the effectiveness of this approach testing dried blood spots from 4 genetically confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values were established on 50,000 healthy newborns (deoxyadenosine <0.09 mol/L, adenosine <1.61 mol/L). We also developed a second tier test to distinguish true positives from false positives and improve the positive predictive value of an initial abnormal result.In the first 18 months, the pilot project has identified a newborn with a genetically confirmed defect in adenosine deaminase (ADA) gene.The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

See 2 more Smart Citations

The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry

Marca

Giocaliere

Malvagia

et al. 2014

Journal of Pharmaceutical and Biomedical Analysis

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“…Since the TREC assay may not reliably detect patients with ADA deficiency [34], we also tested the newborns for ADA deficiency by determining the concentrations of two purine metabolites, Ado and dAdo, using NeoBase2 Non-derivatized MSMS kit (PerkinElmer, Turku, Finland). After we had screened 21,591 newborns, there were no cases showing elevation of Ado and dAdo.…”

Section: Ada Deficiencymentioning

confidence: 99%

Newborn Screening for Severe Combined Immunodeficiency in Taiwan

Chien

Lee

et al. 2017

IJNS

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A study of newborn screening for severe combined immunodeficiency (SCID) by detecting the T-cell receptor excision circle (TRECs) copy number in dried blood spots (DBSs) collected from newborns 3 days of age began in 2010 in Taiwan, and SCID screening was subsequently implemented country-wide in 2012. A total of 920,398 newborns were screened during a period of 78 months. Of these, 175 newborns (0.02%) were requested to undergo an immune function survey, and 136 cases (1 in 6768 newborns) were ultimately diagnosed as having T cell lymphopenia. The screening detected seven cases of typical SCID, with an incidence of 1 in 131,485 newborns (95% confidence interval, 1/63,693~1/271,434). Hematopoietic stem cell transplantation was performed in six patients before overt infection occurred, and the survival rate was 100%. The screening also detected eight cases of SCID variants and 20 cases of 22q11.2 deletion syndrome. Other etiologies of T lymphopenia were identified, and those newborns were evaluated and managed according to their immunological status. Owing to the introduction of newborn screening by measuring the TREC copy number, early administration of treatments became possible for newborns with conditions that put them at risk of primary or secondary immunodeficiency.

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

Kwan

Abraham

Currier

et al. 2014

JAMA

601

569

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IMPORTANCE 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. OBJECTIVES 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. DESIGN Epidemiological and retrospective observational study. SETTING 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. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.

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Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency

Cited by 60 publications

References 23 publications

The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry

The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry

Newborn Screening for Severe Combined Immunodeficiency in Taiwan

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

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