Skip to main content
SpringerLink
Log in

Delayed-onset adenosine deaminase deficiency with a novel synonymous mutation and a case series from China

  • Original Article
  • Published:
World Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Background

Adenosine deaminase (ADA) is a key enzyme in the purine salvage pathway. Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency. To date, few Chinese cases have been reported.

Methods

We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children’s Hospital and summarized the previously published ADA deficiency cases from China in the literature.

Results

Nine patients were identified with two novel mutations (W272X and Q202 =). Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients. The ADA genotype has a major effect on the clinical phenotype. Notably, a novel synonymous mutation (c.606G>A, p.Q202=) was identified in a delayed-onset patient, which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein. Furthermore, the patient showed γδT cells expansion with an increased effect or phenotype, which may be associated with the delayed onset of disease. In addition, we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency. Five patients died with a median age of four months, while two patients received stem cell transplantation and are alive.

Conclusions

This study described the first case series of Chinese ADA-deficient patients. Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations in our patients. We identified a synonymous mutation that affected pre-mRNA splicing in the ADA gene, which had never been reported in ADA deficiency. Furthermore, we reported cerebral aneurysm in a delayed-onset patient for the first time. Further study is warranted to investigate the underlying mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this published article.

References

  1. Sauer AV, Brigida I, Carriglio N, Aiuti A. Autoimmune dysregulation and purine metabolism in adenosine deaminase deficiency. Front Immunol. 2012;3:265.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gaspar HB. Bone marrow transplantation and alternatives for adenosine deaminase deficiency. Immunol Allergy Clin North Am. 2010;30:221–36.

    Article  PubMed  Google Scholar 

  3. Shaw KL, Kohn DB. A tale of two SCIDs. Sci Transl Med. 2011;3:97–36.

    Article  Google Scholar 

  4. Flinn AM, Gennery AR. Adenosine deaminase deficiency: a review. Orphanet J Rare Dis. 2018;13:65–7.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hershfield M. Adenosine Deaminase Deficiency. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993–2023.

  6. Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972;2:1067–9.

    Article  CAS  PubMed  Google Scholar 

  7. Sun Q, Guo J, Hao C, Guo R, Hu X, Chen Y, et al. Whole-exome sequencing reveals two de novo variants in the RBM20 gene in two Chinese patients with left ventricular non-compaction cardiomyopathy. Pediatr Investig. 2020;4:11–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lu XM, Zhu CJ, Zhang XZ, Liu HQ, Sun RP. A case of combined immunodeficiency with adenine deaminase deficiency. J Shandong Univ. 1989;24:87–8 (in Chinese).

    Google Scholar 

  9. Liang WL, Liu CJ, Wu Q, Liu YL, Mao HW. A case of adenosine deaminase deficiency caused by new gene mutation. Chin J Pediatr. 2018;56:636–7 (in Chinese).

    CAS  Google Scholar 

  10. Li T, Lu G, Tao JP, Huang L. A case of severe combined immunodeficiency caused by adenosine deaminase deficiency. Chin Pediatr Emerg. 2020;27:877–8 (in Chinese).

    Google Scholar 

  11. Guan J, Hu Q, Wang L, Zhang T, Cheng H, Zou L. A new ADA gene complex heterozygous mutation causes late onset atypical severe combined immunodeficiency disease. Immunol J. 2021;37:988–94.

    Google Scholar 

  12. Arredondo-Vega FX, Santisteban I, Daniels S, Toutain S, Hershfield MS. Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles. Am J Hum Genet. 1998;63:1049–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hirschhorn R, Tzall S, Ellenbogen A, Orkin SH. Identification of a point mutation resulting in a heat-labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency. J Clin Invest. 1989;83:497–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nakaoka H, Kanegane H, Taneichi H, Miya K, Yang X, Nomura K, et al. Delayed onset adenosine deaminase deficiency associated with acute disseminated encephalomyelitis. Int J Hematol. 2012;95:692–6.

    Article  CAS  PubMed  Google Scholar 

  15. Santisteban I, Arredondo-Vega FX, Kelly S, Loubser M, Meydan N, Roifman C, et al. Three new adenosine deaminase mutations that define a splicing enhancer and cause severe and partial phenotypes: implications for evolution of a CpG hotspot and expression of a transduced ADA cDNA. Hum Mol Genet. 1995;4:2081–7.

    Article  CAS  PubMed  Google Scholar 

  16. Cheng N, Li M, Zhao L, Zhang B, Yang Y, Zheng CH, et al. Comparison and integration of computational methods for deleterious synonymous mutation prediction. Brief Bioinform. 2020;21:970–81.

    Article  CAS  PubMed  Google Scholar 

  17. Hunt RC, Simhadri VL, Iandoli M, Sauna ZE, Kimchi-Sarfaty C. Exposing synonymous mutations. Trends Genet. 2014;30:308–21.

    Article  CAS  PubMed  Google Scholar 

  18. Chen R, Davydov EV, Sirota M, Butte AJ. Nonsynonymous and synonymous coding SNPs show similar likelihood and effect size of human disease association. PLoS One. 2010;5:13574.

    Article  Google Scholar 

  19. Niersch J, Vega-Rubin-de-Celis S, Bazarna A, Mergener S, Jendrossek V, Siveke JT, et al. A BAP1 synonymous mutation results in exon skipping loss of function and worse patient prognosis. Science. 2021;24:102173.

    CAS  Google Scholar 

  20. Li M, Lu X, Dong J, Yao Z, Wu Y, Rao H, et al. A synonymous mutation in exon 39 of FBN1 causes exon skipping leading to Marfan syndrome. Genomics. 2020;112:3856–61.

    Article  CAS  PubMed  Google Scholar 

  21. Ito K, Patel PN, Gorham JM, McDonough B, DePalma SR, Adler EE, et al. Identification of pathogenic gene mutations in LMNA and MYBPC3 that alter RNA splicing. Proc Natl Acad Sci U S A. 2017;114:7689–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang R, Chen Z, Song Q, Wang S, Liu Z, Zhao X, et al. Identification of seven exonic variants in the SLC4A1, ATP6V1B1, and ATP6V0A4 genes that alter RNA splicing by minigene assay. Hum Mutat. 2021;42:1153–64.

    Article  CAS  PubMed  Google Scholar 

  23. Teraoka SN, Telatar M, Becker-Catania S, Liang T, Onengut S, Tolun A, et al. Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences. Am J Hum Genet. 1999;64:1617–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cagdas D, Gur Cetinkaya P, Karaatmaca B, Esenboga S, Tan C, Yılmaz T, et al. ADA deficiency: evaluation of the clinical and laboratory features and the outcome. J Clin Immunol. 2018;38:484–93.

    Article  CAS  PubMed  Google Scholar 

  25. Antonioli L, Csóka B, Fornai M, Colucci R, Kókai E, Blandizzi C, et al. Adenosine and inflammation: what’s new on the horizon? Drug Discov Today. 2014;19:1051–68.

    Article  CAS  PubMed  Google Scholar 

  26. Novitskiy SV, Ryzhov S, Zaynagetdinov R, Goldstein AE, Huang Y, Tikhomirov OY, et al. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood. 2008;112:1822–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Karmouty Quintana H, Zhong H, Acero L, Weng T, Melicoff E, West JD, et al. The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease. FASEB J. 2012;26:2546–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Huang L, Fan J, Chen Y, Wang J. Inhibition of A2B adenosine receptor attenuates intestinal injury in a rat model of necrotizing enterocolitis. Mediators Inflamm. 2020;2020:1562973.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Merighi S, Bencivenni S, Vincenzi F, Varani K, Borea PA, Gessi S. A2B adenosine receptors stimulate IL-6 production in primary murine microglia through p38 MAPK kinase pathway. Pharmacol Res. 2017;117:9–19.

    Article  CAS  PubMed  Google Scholar 

  30. Marucci G, Ben DD, Lambertucci C, Navia AM, Spinaci A, Volpini R, et al. Combined therapy of A1AR agonists and A2AAR antagonists in neuroinflammation. Molecules. 2021;26:1188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Meyts I, Aksentijevich I. Deficiency of adenosine deaminase 2 (DADA2): updates on the phenotype, genetics, pathogenesis, and treatment. J Clin Immunol. 2018;38:569–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 2014;370:911–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Navon Elkan P, Pierce SB, Segel R, Walsh T, Barash J, Padeh S, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med. 2014;370:921–31.

    Article  PubMed  Google Scholar 

  34. Lee PY, Aksentijevich I, Zhou Q. Mechanisms of vascular inflammation in deficiency of adenosine deaminase 2 (DADA2). Semin Immunopathol. 2022;44:269–80.

    Article  CAS  PubMed  Google Scholar 

  35. Kaljas Y, Liu C, Skaldin M, Wu C, Zhou Q, Lu Y, et al. Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells. Cell Mol Life Sci. 2017;74:555–70.

    Article  CAS  PubMed  Google Scholar 

  36. Schena F, Penco F, Volpi S, Pastorino C, Caorsi R, Kalli F, et al. Dysregulation in B-cell responses and T follicular helper cell function in ADA2 deficiency patients. Eur J Immunol. 2021;51:206–19.

    Article  CAS  PubMed  Google Scholar 

  37. Yap JY, Moens L, Lin M, Kane A, Kelleher A, Toong C, et al. Intrinsic defects in B cell development and differentiation, T cell exhaustion and altered unconventional T cell generation characterize human adenosine deaminase type 2 deficiency. J Clin Immunol. 2021;41:1915–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Benveniste P, Zhu W, Cohen A. Interference with thymocyte differentiation by an inhibitor of S-adenosylhomocysteine hydrolase. J Immunol. 1995;155:536–44.

    Article  CAS  PubMed  Google Scholar 

  39. Gangi-Peterson L, Sorscher DH, Reynolds JW, Kepler TB, Mitchell BS. Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination. J Clin Invest. 1999;103:833–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Apasov SG, Blackburn MR, Kellems RE, Smith PT, Sitkovsky MV. Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling. J Clin Invest. 2001;108:131–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Aldrich MB, Chen W, Blackburn MR, Martinez-Valdez H, Datta SK, Kellems RE. Impaired germinal center maturation in adenosine deaminase deficiency. J Immunol. 2003;171:5562–70.

    Article  CAS  PubMed  Google Scholar 

  42. Zheng J, Liu Y, Lau Y, Tu W. γδ-T cells: an unpolished sword in human anti-infection immunity. Cell Mol Immunol. 2013;10:50–7.

    Article  CAS  PubMed  Google Scholar 

  43. Ou L, Wang H, Liu Q, Zhang J, Lu H, Luo L, et al. Dichotomous and stable gamma delta T-cell number and function in healthy individuals. J Immunother Cancer. 2021;9:e002274.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tuovinen EA, Pöysti S, Hamdan F, Le KM, Keskitalo S, Turunen T, et al. Characterization of expanded gamma delta T cells from atypical X-SCID patient reveals preserved function and IL2RG-mediated signaling. J Clin Immunol. 2023;43:358–70.

    Article  CAS  PubMed  Google Scholar 

  45. Garcillan B, Mazariegos MS, Fisch P, Res PC, Muñoz-Ruiz M, Gil J, et al. Enrichment of the rare CD4+ γδ T-cell subset in patients with atypical CD3δ deficiency. J Allergy Clin Immunol. 2014;133:1205–8.

    Article  CAS  PubMed  Google Scholar 

  46. Ehl S, Schwarz K, Enders A, Duffner U, Pannicke U, Kühr J, et al. A variant of SCID with specific immune responses and predominance of gamma delta T cells. J Clin Invest. 2005;115:3140–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tometten I, Felgentreff K, Hönig M, Hauck F, Albert MH, Niehues T, et al. Increased proportions of γδ T lymphocytes in atypical SCID associate with disease manifestations. Clin Immunol. 2019;201:30–4.

    Article  CAS  PubMed  Google Scholar 

  48. Pellicci DG, Koay HF, Berzins SP. Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge. Nat Rev Immunol. 2020;20:756–70.

    Article  CAS  PubMed  Google Scholar 

  49. Kim VH, Pham-Huy A, Grunebaum E. Neutropenia among patients with adenosine deaminase deficiency. J Allergy Clin Immunol. 2019;143:403–5.

    Article  PubMed  Google Scholar 

  50. Sauer AV, Mrak E, Jofra Hernandez R, Zacchi E, Cavani F, Casiraghi M, et al. ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency. Blood. 2009;114:3216–26.

    Article  CAS  PubMed  Google Scholar 

  51. Albuquerque W, Gaspar HB. Bilateral sensorineural deafness in adenosine deaminase-deficient severe combined immunodeficiency. J Pediatr. 2004;144:278–80.

    Article  PubMed  Google Scholar 

  52. Sauer AV, Hernandez RJ, Fumagalli F, Bianchi V, Poliani PL, Dallatomasina C, et al. Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients. Sci Rep. 2017;7:40136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Booth C, Algar VE, Xu-Bayford J, Fairbanks L, Owens C, Gaspar HB. Non-infectious lung disease in patients with adenosine deaminase deficient severe combined immunodeficiency. J Clin Immunol. 2012;32:449–53.

    Article  CAS  PubMed  Google Scholar 

  54. Kühl JS, Schwarz K, Münch A, Schmugge M, Pekrun A, Meisel C, et al. Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID). Klin Padiatr. 2011;223:85–9.

    Article  PubMed  Google Scholar 

  55. Nikolajeva O, Worth A, Hague R, Martinez-Alier N, Smart J, Adams S, et al. Adenosine deaminase deficient severe combined immunodeficiency presenting as atypical haemolytic uraemic syndrome. J Clin Immunol. 2015;35:366–72.

    Article  CAS  PubMed  Google Scholar 

  56. Kesserwan C, Sokolic R, Cowen EW, Garabedian E, Heselmeyer-Haddad K, Lee CCR, et al. Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency. J Allergy Clin Immunol. 2012;129:762–9.e1.

    Article  CAS  PubMed  Google Scholar 

  57. Flinn AM, Flood T, Prendiville T, Gennery AR, Leahy TR. Adenosine deaminase deficient SCID with myocardial hypertrophy. J Clin Immunol. 2021;41:1128–30.

    Article  PubMed  Google Scholar 

  58. Kohn DB, Hershfield MS, Puck JM, Aiuti A, Blincoe A, Gaspar HB, et al. Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. J Allergy Clin Immunol. 2019;143:852–63.

    Article  PubMed  Google Scholar 

  59. Kohn DB, Booth C, Shaw KL, Xu-Bayford J, Garabedian E, Trevisan V, et al. Autologous ex vivo lentiviral gene therapy for adenosine deaminase deficiency. N Engl J Med. 2021;384:2002–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Argudo-Ramírez A, Martín-Nalda A, Marín-Soria JL, López-Galera RM, Pajares-García S, González de Aledo-Castillo JM, et al. First universal newborn screening program for severe combined immunodeficiency in Europe Two-years experience in Catalonia (Spain). Front Immunol. 2019;10:2406.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Göngrich C, Ekwall O, Sundin M, Brodszki N, Fasth A, Marits P, et al. First year of TREC-based national SCID screening in Sweden. Int J Neonatal Screen. 2021;7:59.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Chien Y, Chiang S, Chang K, Yu H, Lee W, Tsai L, et al. Incidence of severe combined immunodeficiency through newborn screening in a Chinese population. J Formos Med Assoc. 2015;114:12–6.

    Article  PubMed  Google Scholar 

  63. Amatuni GS, Currier RJ, Church JA, Bishop T, Grimbacher E, Nguyen AA, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California, 2010–2017. Pediatrics. 2019;143:e20182300.

    Article  PubMed  Google Scholar 

  64. Audrain MAP, Léger AJC, Hémont CAF, Mirallié SM, Cheillan D, Rimbert MGM, et al. Newborn screening for severe combined immunodeficiency: analytic and clinical performance of the T cell receptor excision circle assay in France (DEPISTREC study). J Clin Immunol. 2018;38:778–86.

    Article  PubMed  Google Scholar 

  65. Guo J, Liu P, Chen L, Lv H, Li J, Yu W, et al. National rare diseases registry system (NRDRS): China’s first nation-wide rare diseases demographic analyses. Orphanet J Rare Dis. 2021;16:515.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Cuvelier GDE, Logan BR, Prockop SE, Buckley RH, Kuo CY, Griffith LM, et al. Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC. Blood. 2022;140:685–705.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the patients and their families for their collaboration. We thank all the members of clinical team who provided care for patients.

Funding

This work was supported in part by the National Natural Science Foundation of China (81971547 and 81900136), Beijing Hospitals Authority’s Ascent Plan (DFL20221001), National Key Research and Development Program of China (2021YFC2702005), and Wu Jieping Medical Foundation (320.6750.2022–03-53).

Author information

Authors and Affiliations

  1. Department of Immunology, Beijing Children’s Hospital, Capital Medical University, National Center for Children′s Health, No. 56 Nan Lishi Road, Xicheng District, Beijing, 100045, China

    Yue Zhang, Zhou Shu, Yan Li, Fei Sun, Tong-Xin Han & Hua-Wei Mao

  2. Hematology Oncology Center, Henan Children’s Hospital, Children’s Hospital Affiliated of Zhengzhou University, Zhengzhou Children’s Hospital, Zhengzhou, China

    Wei Liu

  3. Hematologic Disease Laboratory, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

    Zhi-Gang Li

  4. Hematology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 Nan Lishi Road, Xicheng District, Beijing, 100045, China

    Zhi-Gang Li & Tian-You Wang

  5. Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Capital Medical University, Beijing, China

    Zhi-Gang Li & Tian-You Wang

  6. Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China

    Zhi-Gang Li, Hua-Wei Mao & Tian-You Wang

Authors
  1. Yue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhou Shu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhi-Gang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tong-Xin Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hua-Wei Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tian-You Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ZY and LW contributed equally to this work. ZY and LW contributed to original draft. SZ contributed to reviewing and editing. LY, SF and HTX contributed to data curation. LZG contributed to formal analysis. MHW and WTY guided the study and revised the manuscript critically. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hua-Wei Mao or Tian-You Wang.

Ethics declarations

Ethical approval

This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Beijing Children’s Hospital, Capital Medical University (2021-E-192-R). Informed consent to participate in the study has been obtained from the participants or their parent or legal guardian in the case of children under 16.

Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. The authors have no conflict of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file 1 (MP4 147439 KB)

Supplementary file 2 (PDF 400 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Liu, W., Shu, Z. et al. Delayed-onset adenosine deaminase deficiency with a novel synonymous mutation and a case series from China. World J Pediatr 19, 687–700 (2023). https://doi.org/10.1007/s12519-023-00729-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12519-023-00729-3

Keywords

Search

Navigation