ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome

Çağdaş, Deniz; Çetinkaya, Pınar Gür; Karaatmaca, Betül; Esenboğa, Saliha; Tan, Çağman; Yılmaz, Togay; Gümüş, Ersin; Barış, Safa; Kuşkonmaz, Barış; Özgür, Tuba Turul; Bali, Pawan; Santistéban, Inés; Orhan, Dıclehan; Yüce, Aysel; Çetinkaya, Duygu Uçkan; Boztuğ, Kaan; Hershfield, Michael S.; Sanal, Özden; Tezcan, İlhan

doi:10.1007/s10875-018-0496-9

Cited by 29 publications

(15 citation statements)

References 28 publications

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“…ADA-enzyme and metabolite levels were compatible seen in SCID form of ADA deficiency (Duke University). 20 In a series of 13 patients reported from our center, another patient with the same mutation with our patient had also marked neutropenia, 15 since he had underwent HSCT, we could not evaluate CD40/CD40L expression of him.…”

Section: Discussionmentioning

confidence: 78%

“…Prolonged neutropenia in patients with ADA deficiency is a rare and interesting finding and reported before in our unit in another patient with the same molecular defect. 15 Myeloid dysplasia and bone marrow hypocellularity have been previously reported in ADA-deficient SCID patients. In these patients, neutropenia may be due to accumulating toxic metabolites, not just autoantibodies against neutrophils.…”

Section: Discussionmentioning

confidence: 88%

See 1 more Smart Citation

In case of recurrent wheezing and bronchiolitis: Think again, it may be a primary immunodeficiency

Özbek

Ayvaz

Esenboğa

et al. 2022

Asian Pac J Allergy Immunol

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Background: Wheezing, starting early in life, is a heterogeneous medical condition caused by airway obstruction due to different underlying mechanisms. Primary immunodeficiencies are also among the risk factors that cause wheezing and recurrent bronchiolitis. ADA deficiency is a primary immunodeficiency, also a rare metabolic disease associated with multisystemic clinical findings.Objective: This report will be helpful for adressing the importance of thinking primary immunodeficiency in case of wheezing and recurret bronchiolitis. Methods:The patient was diagnosed by using a targeted next generation sequencing PID panel. Lymphocyte subsets were measured by flow-cytometry.Results: Here we present an infant with ADA deficiency who admitted with wheezing and recurrent bronchiolitis as the first presentation. He was found to have wheezing, relative CD4+ T cell deficiency, and prolonged neutropenia. Conclusion:Primary immunodeficiencies including ADA deficiency should be considered in infants with wheezing, recurrent bronchiolitis, lymphopenia and neutropenia.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 88%

In case of recurrent wheezing and bronchiolitis: Think again, it may be a primary immunodeficiency

Özbek

Ayvaz

Esenboğa

et al. 2022

Asian Pac J Allergy Immunol

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“…Long-term outcomes for ADA-deficient patients receiving different therapies have been reported from single-center 17,42,43 (H. B. Gaspar, unpublished data; June 17, 2018) and multicenter 44,45 studies. HSC-GT has been approved for clinical use in the European Union, 46 and promising results from lentivirus vector-based HSC-GT studies are emerging.…”

Section: Abbreviations Usedmentioning

confidence: 99%

“…[33][34][35]37 This might be related to a progressive decrease in lymphocyte counts and function during long-term ERT, which has been documented at several treatment centers. 17,42,43,[64][65][66][67] The reasons for this decrease are uncertain but were apparently not related to loss of the biochemical action or a change in the pharmacokinetics of Adagen or development of neutralizing antibody.…”

Section: Ertmentioning

confidence: 99%

Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency

Kohn

Hershfield

Puck

et al. 2019

Journal of Allergy and Clinical Immunology

113

104

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Inherited defects in adenosine deaminase (ADA) cause a subtype of severe combined immunodeficiency (SCID) known as severe combined immune deficiency caused by adenosine deaminase defects (ADA-SCID). Most affected infants can receive a diagnosis while still asymptomatic by using an SCID newborn screening test, allowing early initiation of therapy. We review the evidence currently available and propose a consensus management strategy. In addition to treatment of the immune deficiency seen in patients with ADA-SCID, patients should be followed for specific noninfectious respiratory, neurological, and biochemical complications associated with ADA deficiency. All patients should initially receive enzyme replacement therapy (ERT), followed by definitive treatment with either of 2 equal first-line options. If an HLA-matched sibling donor or HLA-matched family donor is available, allogeneic hematopoietic stem cell transplantation (HSCT) should be pursued. The excellent safety and efficacy observed in more than 100 patients with ADA-SCID who received gammaretrovirus- or lentivirus-mediated autologous hematopoietic stem cell gene therapy (HSC-GT) since 2000 now positions HSC-GT as an equal alternative. If HLA-matched sibling donor/HLA-matched family donor HSCT or HSC-GT are not available or have failed, ERT can be continued or reinstituted, and HSCT with alternative donors should be considered. The outcomes of novel HSCT, ERT, and HSC-GT strategies should be evaluated prospectively in "real-life" conditions to further inform these management guidelines.

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“…Several single-center [27][28][29][30] and multicenter studies [21,31,32] have highlighted the efficiency of HSCT, in particular from HLA-matched sibling donors (MSDs) and HLA-matched family donors (MFDs), providing long-term correction of the immune and metabolic abnormalities in ADA-deficient patients. The largest study to date is a multicenter study investigating the outcome of HSCT in 106 ADA-deficient SCID patients [21].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Immune Recovery After Hematopoietic Stem Cell Transplantation for ADA Deficiency: a Single-Center Experience

et al. 2021

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Unconditioned hematopoietic stem cell transplantation (HSCT) is the recommended treatment for patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency with an HLA-matched sibling donor (MSD) or family donor (MFD). Improved overall survival (OS) has been reported compared to the use of unrelated donors, and previous studies have demonstrated that adequate cellular and humoral immune recovery can be achieved even in the absence of conditioning. Detailed insight of the long-term outcome is still limited. We aim to address this by studying a large single-center cohort of 28 adenosine deaminase-deficient patients who underwent a total of 31 HSCT procedures, of which more than half were unconditioned. We report an OS of 85.7% and event-free survival of 71% for the entire cohort, with no statistically significant differences after procedures using related or unrelated HLA-matched donors. We find that donor engraftment in the myeloid compartment is significantly diminished in unconditioned procedures, which typically use a MSD or MFD. This is associated with poor metabolic correction and more frequent failure to discontinue immunoglobulin replacement therapy. Approximately one in four patients receiving an unconditioned procedure required a second procedure, whereas the use of reduced intensity conditioning (RIC) prior to allogeneic transplantation improves the long-term outcome by achieving better myeloid engraftment, humoral immune recovery, and metabolic correction. Further longitudinal studies are needed to optimize future management and guidelines, but our findings support a potential role for the routine use of RIC in most ADA-deficient patients receiving an HLA-identical hematopoietic stem cell transplant, even when a MSD or MFD is available.

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ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome

Cited by 29 publications

References 28 publications

In case of recurrent wheezing and bronchiolitis: Think again, it may be a primary immunodeficiency

In case of recurrent wheezing and bronchiolitis: Think again, it may be a primary immunodeficiency

Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency

Long-Term Immune Recovery After Hematopoietic Stem Cell Transplantation for ADA Deficiency: a Single-Center Experience

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