Managing Newborn Screening for SCID in a Referral Centre

Reid, Brenda; Ovadia, Adi; Schejter, Yael Dinur

doi:10.14785/lymphosign-2017-0005

Cited by 4 publications

(1 citation statement)

References 8 publications

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“…However, this may pose an ethical conundrum since some jurisdictions, such as the Netherlands, do not allow the screening and reporting of diseases for which there is no cure. In Ontario, the finding of a positive SCID newborn screen, regardless of underlying cause, triggers urgent follow-up evaluation in accordance with our Ministry of Health-approved algorithm for assessment and treatment of such cases (30).…”

Section: Discussionmentioning

confidence: 99%

Ataxia Telangiectasia Diagnosed on Newborn Screening–Case Cohort of 5 Years' Experience

et al. 2019

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Ataxia telangiectasia (AT) is a genetic condition caused by mutations involving ATM (Ataxia Telangiectasia Mutated). This gene is responsible for the expression of a DNA double stranded break repair kinase, the ATM protein kinase. The syndrome encompasses combined immunodeficiency and various degrees of neurological abnormalities and increased risk of malignancy. Typically, patients present early in life with delay in neurological milestones, but very infrequently, with life threatening infections typical of a profound T cell deficiency. It would therefore be unexpected to identify this condition immediately after birth using T cell receptor excision circle (TREC)-based newborn screening (NBS) for SCID. We sought to evaluate the frequency of AT detected by NBS, and to assess immunity as well as the genetic aberrations associated with this early presentation. Here, we describe the clinical, laboratory, and genetic features of patients diagnosed with AT through the Ontario NBS program for SCID, and followed in our center since its inception in 2013. Four patients were diagnosed with AT as a result of low TRECs on NBS. In each case, whole exome sequencing was diagnostic. All of our patients had compound heterozygous mutations involving the FRAP-ATM-TRRAP (FAT) domain of the ATM gene, which appears critical for kinase activity and is highly sensitive to mutagenesis. Our patients presented with profound lymphopenia involving both B and T cells. The ratio of naïve/memory CD45+RA/RO T cells population was variable. T cell repertoire showed decreased T cell diversity. Two out of four patients had decreased specific antibody response to vaccination and hypogammaglobulinemia requiring IVIG replacement. In two patients, profound decreased responses to phytohemagglutinin stimulation was observed. In the other two patients, the initial robust response declined with time. In summary, the rate of detection of AT through NBS had been surprisingly high at our center. One case was identified per year, while the total rate for SCID has been five new cases per year. This early detection may allow for better prospective evaluation of AT shortly after birth, and may assist in formulating early and more effective interventions both for the neurological as well as the immune abnormalities in this syndrome.

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Section: Discussionmentioning

confidence: 99%

Ataxia Telangiectasia Diagnosed on Newborn Screening–Case Cohort of 5 Years' Experience

et al. 2019

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Report of the Canadian Expert Committee on the management of ADA deficiency

et al. 2020

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Adenosine deaminase (ADA) deficiency is a form of severe combined immunodeficiency. Aberrant mutations in the ADA gene result in loss of ADA activity and the toxic accumulation of metabolites that damage both immune and non-immune organs. While patients with complete ADA deficiency present during infancy with failure to thrive, recurrent bacterial, viral and fungal infections, those with incomplete (partial) deficiency may present at a later age with milder symptoms associated with reduced T, B, and NK cell subpopulations. Based on experience in Canadian centres, we provide management guidelines for patients with ADA deficiency, including a treatment algorithm for use of hematopoietic stem cell transplantation, gene therapy, and enzyme replacement therapy.

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An unusual presentation of DiGeorge syndrome

et al. 2022

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Introduction: DiGeorge syndrome is a heterogenous disorder with various clinical presentations. Common features of 22q11.2 deletion syndrome include thymic hypoplasia T-cell lymphopenia, conotruncal heart defects, facial dysmorphism, cleft palate, developmental delay and hypoparathyroidism. The severity of the condition varies, however typical presentation includes congenital heart defects and characteristic facial features. Isolated hypocalcemia in DiGeorge syndrome is rarely seen in as the sole manifestation in older teenagers of adults Aim: To report a case of an atypical presentation of DiGeorge syndrome Results: We report here a case of an infant who was diagnosed with DiGeorge syndrome with seizures being the only clinical manifestation displayed by the patient. He was found to have low TRECs on a newborn screen for severe combined immunodeficiency. He did not have facial dysmorphism nor cardiac defect. Conclusion: Our case showed that severe hypocalcemia can be the only presenting symptom in DiGeorge syndrome, based on this case we recommend physicians to test for calcium levels and PTH at the first encounter with a positive NBS for SCID.

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Managing Newborn Screening for SCID in a Referral Centre

Cited by 4 publications

References 8 publications

Ataxia Telangiectasia Diagnosed on Newborn Screening–Case Cohort of 5 Years' Experience

Ataxia Telangiectasia Diagnosed on Newborn Screening–Case Cohort of 5 Years' Experience

Report of the Canadian Expert Committee on the management of ADA deficiency

An unusual presentation of DiGeorge syndrome

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