Evaluation of Patients with Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency: A Single-Center Experience

Öz

Objective: This study aimed to evaluate the clinical, immunological, and prognostic features of seven patients diagnosed with Adenosine Deaminase Deficiency Severe Combined Immunodeficiency (ADA-SCID) at Marmara University. The aim of this study was to enhance the recognition and management of this condition, which is characterized by impaired lymphocyte development and early severe infections. Methods: This retrospective study included seven patients with ADA-SCIDs who were monitored from 2012 to 2024. Patient data, including demographics, clinical findings, laboratory results, and imaging, were retrieved from hospital records. Diagnostic criteria focused on ADA enzyme activity and genetic mutations. Treatment regimens, such as immunoglobulin replacement, antimicrobial prophylaxis, enzyme replacement therapy, and hematopoietic stem cell transplantation (HSCT), were documented. Statistical analyses were performed using descriptive methods. Results: The cohort (6 males, 1 female) presented a median age at diagnosis of 3 months. Consanguinity was observed in 86% of cases. Key symptoms included lymphopenia, recurrent infections, thymus absence, and systemic manifestations. Six patients received HSCT, and two underwent matched donor transplantation. One patient received gene therapy because of the absence of a matched donor. Opportunistic infections were prevalent, including cytomegalovirus and recurrent skin infections noted. Overall, two patients died of post-HSCT complications. Conclusions: ADA-SCID is a life-threatening condition characterized by early severe infections and systemic manifestations. Early diagnosis and tailored treatment, including HSCT and gene therapy, are essential for improving survival outcomes. This study emphasizes the importance of early diagnosis to improve the survival and management outcomes of patients with ADA-SCID.

Anahtar Kelimeler

• Adenosine Deaminase Deficiency
• Child
• Hematopoietic Stem Cell Transplantation Inborn Errors of Immunity
• Lymphopenia
• Severe Combined İmmunodeficiency

Kaynakça

1. Hershfield M, Tarrant T. Adenosine deaminase deficiency. GeneReviews®[Internet], 2024. google scholar
2. Grunebaum, E. et al. Updated management guidelines for adenosine deaminase deficiency. The Journal of Allergy and Clinical Immunology: In Practice, 2023. 11(6): p. 1665-1675. google scholar
3. Kuo, C.Y., et al. Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID) in the US Immunodeficiency Network (USIDNet) Registry. Journal of clinical immunology, 2020. 40: p. 1124-1131. google scholar
4. Dqbrowska-Leonik, N. et al., National experience with adenosine deaminase deficiency related SCID in Polish children. Frontiers in Immunology, 2023. 13: p. 1058623. google scholar
5. Secord E, Hartog NL. Review of treatment for adenosine deaminase deficiency (ADA) severe combined immunodeficiency (SCID). Therapeutics and Clinical Risk Management, 2022: p. 939-944. google scholar
6. Cuvelier, G.D., et al., Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC. Blood, 2022. 140(7): p. 685-705. google scholar
7. Besci, Ö., et al. Reference values for T and B lymphocyte subpopulations in Turkish children and adults. Turkish journal of medical sciences, 2021. 51(4): p. 1814-1824. google scholar
8. Jamovi, P., Jamovi (Version 2.3)[Computer Software]. 2022. google scholar

9. Dvorak, C. C. et al. The diagnosis of severe combined immunodeficiency (SCID): the primary immune deficiency treatment consortium (PIDTC) 2022 definitions. Journal of Allergy and Clinical Immunology, 2023. 151(2): p. 539-546. google scholar
10. Baffelli, R., et al. Diagnosis, treatment and long-term follow-up of patients with ADA deficiency: a single-center experience. Journal of clinical immunology, 2015. 35: p. 624-637. google scholar
11. Baris, S., et al., The Middle East and North Africa diagnosis and management guidelines for inborn errors of immunity. The Journal of Allergy and Clinical Immunology: In Practice, 2023. 11(1): p. 158-180. e11. google scholar
12. Routes J, Verbsky J. Newborn screening for severe combined immunodeficiency. Current Allergy and Asthma Reports. 2018;18:1-7. google scholar
13. Kwan, A. et al., Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. Jama, 2014. 312(7): p. 729-738. google scholar
14. Flinn AM, Gennery AR. Adenosine deaminase deficiency: a review. Orphanet J Rare Dis., 2018. 13: p. 1-7. google scholar
15. Bradford, K.L., et al. Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID): molecular pathogenesis and clinical manifestations. Journal of clinical immunology, 2017. 37: p. 626-637. google scholar
16. Verhagen, M. V. et al. Chest radiographs for distinguishing ADA-SCID from other forms of SCID. Journal of Clinical Immunology, 2020. 40: p. 259-266. google scholar
17. Minagawa, H., et al. Skeletal dysplasia in adenosine deaminase deficiency. Pediatrics International, 2022. 64(1): p. e15214. google scholar
18. Rogers, M. H. et al. Cognitive and behavioral abnormalities in adenosine deaminase deficient severe combined immunodeficiency. The Journal of pediatrics, 2001. 139(1): p. 44-50. google scholar
19. Kohn, D. B. et al. Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. Journal of Allergy and Clinical Immunology, 2019. 143(3): p. 852-863. google scholar
20. Bousfiha, A., et al., The 2022 update of IUIS phenotypical classification for human inborn errors of immunity. Journal of clinical immunology, 2022. 42(7): p. 1508-1520. google scholar