Delayed-Onset ADA1 (ADA) Deficiency Not Detected by TREC Screen

American Academy of Pediatrics (AAP) - Tập 147 Số 6 - 2021
Basil M. Kahwash1,2, Jennifer R. Yonkof1,2, Roshini S. Abraham2, Peter Mustillo2, Rolla Abu‐Arja2, Hemalatha G. Rangarajan2, Rebecca Scherzer2
1Division of Allergy and Immunology, Department of Otolaryngology, College of Medicine, The Ohio State University, Columbus, Ohio; and
2Nationwide Children's Hospital, Columbus, Ohio

Tóm tắt

A 9-month-old boy presented to a community pediatrician with a recent history of failure to thrive. Workup revealed neutropenia and lymphopenia. Subsequent admission for fever and pneumonia revealed an absolute neutrophil count of 860 and absolute lymphocyte count of 214. Lymphopenia affected all lymphocyte subsets and his naïve and memory CD4+ T-cell ratio was inverted for age. Immunoglobulin levels were normal for age, and tetanus and diphtheria antibody titers were protective. The profound lymphopenia raised suspicion for severe combined immunodeficiency (SCID), despite a normal newborn screening by T-cell receptor excision circle analysis. He did not have a previous history of recurrent fevers or infections, had attended day care, and had received all age-appropriate vaccines. He subsequently was diagnosed with Pneumocystis jirovecii pneumonia, adenovirus upper respiratory infection, and rotaviral diarrhea. An enzyme assay revealed absent adenosine deaminase (ADA) activity and elevated erythrocyte deoxyadenosine nucleotides. With genetic sequencing, 2 pathogenic variants in the ADA gene were confirmed. Acute management of ADA-SCID is aimed at restoration of enzyme activity, followed by curative therapy. The patient is currently on immunoglobulin therapy and recombinant ADA (Revcovi), with an excellent immune response, while awaiting sibling hematopoietic cell transplant from a matched sibling. Hypomorphic ADA variants can present with delayed-onset SCID, and some of these patients are missed by SCID newborn screening. A careful review of a complete blood cell count might offer clues and promote confirmatory diagnostic investigation.

Từ khóa


Tài liệu tham khảo

Heimall, 2017, Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study, Blood, 130, 2718, 10.1182/blood-2017-05-781849

Kwan, 2014, Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. [published correction appears in JAMA. 2014;312(20):2169], JAMA, 312, 729, 10.1001/jama.2014.9132

Kubiak, 2014, Fiscal implications of newborn screening in the diagnosis of severe combined immunodeficiency, J Allergy Clin Immunol Pract, 2, 697, 10.1016/j.jaip.2014.05.013

Amatuni, 2019, Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California, 2010-2017, Pediatrics, 143, e20182300, 10.1542/peds.2018-2300

la Marca, 2013, Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency, J Allergy Clin Immunol, 131, 1604, 10.1016/j.jaci.2012.08.054

Bradford, 2017, Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID): molecular pathogenesis and clinical manifestations, J Clin Immunol, 37, 626, 10.1007/s10875-017-0433-3

Cagdas, 2018, ADA deficiency: evaluation of the clinical and laboratory features and the outcome, J Clin Immunol, 38, 484, 10.1007/s10875-018-0496-9

Kohn, 2019, Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency, J Allergy Clin Immunol, 143, 852, 10.1016/j.jaci.2018.08.024

Malphettes, 2009, Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect, Clin Infect Dis, 49, 1329, 10.1086/606059

Sontag, 2005, Two-tiered immunoreactive trypsinogen-based newborn screening for cystic fibrosis in Colorado: screening efficacy and diagnostic outcomes, J Pediatr, 147, S83, 10.1016/j.jpeds.2005.08.005

Sarafoglou, 2012, Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia, Pediatrics, 130, 10.1542/peds.2012-1219

Adhikari, 2020, The role of exome sequencing in newborn screening for inborn errors of metabolism, Nat Med, 26, 1392, 10.1038/s41591-020-0966-5

Thông tin
Thông tin xuất bản

American Academy of Pediatrics (AAP)

Tập 147 Số 6

Thông tin tác giả