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Unreported Missense Mutation in the Dimerization Domain of ADA2 Leads to ADA2 Deficiency Associated with Severe Oral Ulcers and Neutropenia in a Female Somalian Patient—Addendum to the Genotype-Phenotype Puzzle

  • Lisa Göschl
  • Stefan Winkler
  • Jasmin Dmytrus
  • Raul Jimenez Heredia
  • Heimo Lagler
  • Michael Ramharter
  • Clemens Scheinecker
  • Michael Bonelli
  • Klaus Schmetterer
  • Winfried F. Pickl
  • Katharina Grabmeier-Pfistershammer
  • Michael S. Hershfield
  • Kaan Boztug
  • Elisabeth Förster-WaldlEmail author
  • Guido A. Gualdoni
Letter to Editor
  • 21 Downloads

To the Editor,

ADA2 (previously known as CECR1, cat eye syndrome chromosome region, candidate 1) mutations encoding adenosine deaminase 2 (ADA2) were found to cause the first molecularly defined monogenic vasculitis syndrome [1, 2]. Initial patient reports described the condition as partially mimicking polyarteritis nodosa (PAN) with vasculitis and rashes in addition to systemic inflammation [3, 4]. However, subsequent publications unveiled a remarkable pleiotropy of this condition with affections of multiple organ systems, including the skin, the nervous system, the kidneys, and the gastrointestinal tract [4]. Hematological involvement can manifest as severe cytopenia and can also include immunological features like hypogammaglobulinemia and deficiencies in NK cells, T cells, and B cells, which may partially mimic a common variable immunodeficiency syndrome [4, 5]. The autosomal recessive disease is driven by a loss of function of the enzymatic capacity of the mainly extracellular...

Notes

Funding Information

This study was partially funded by the Jeffrey Modell Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10875_2019_700_MOESM1_ESM.docx (19 kb)
ESM 1 (DOCX 19 kb)

References

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    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.CrossRefGoogle Scholar
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    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.CrossRefGoogle Scholar
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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Lisa Göschl
    • 1
  • Stefan Winkler
    • 2
  • Jasmin Dmytrus
    • 3
    • 4
  • Raul Jimenez Heredia
    • 3
    • 4
  • Heimo Lagler
    • 2
  • Michael Ramharter
    • 2
    • 9
    • 10
  • Clemens Scheinecker
    • 1
  • Michael Bonelli
    • 1
  • Klaus Schmetterer
    • 5
  • Winfried F. Pickl
    • 6
  • Katharina Grabmeier-Pfistershammer
    • 6
  • Michael S. Hershfield
    • 7
  • Kaan Boztug
    • 3
    • 4
    • 8
    • 11
  • Elisabeth Förster-Waldl
    • 8
    • 12
    • 14
    Email author
  • Guido A. Gualdoni
    • 2
    • 13
  1. 1.Division of Rheumatology, Department of Medicine IIIMedical University of ViennaViennaAustria
  2. 2.Division of Infectious Diseases and Tropical Medicine, Department of Medicine IMedical University of ViennaViennaAustria
  3. 3.CeMM Research Center for Molecular Medicine of the Austrian Academy of ScienceViennaAustria
  4. 4.Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria
  5. 5.Department of Laboratory MedicineMedical University of ViennaViennaAustria
  6. 6.Institute of Immunology, Centre of Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
  7. 7.Department of Medicine and BiochemistryDuke University Medical CenterDurhamUSA
  8. 8.Department of Pediatrics and Adolescent MedicineMedical University of ViennaViennaAustria
  9. 9.Department of Tropical Medicine, Bernhard Nocht Institute for Tropical MedicineHamburgGermany
  10. 10.First Department of MedicineUniversity Medical Center Hamburg-EppendorfHamburgGermany
  11. 11.Children’s Cancer Research Institute and St. Anna Kinderspital, Department of PediatricsMedical University of ViennaViennaAustria
  12. 12.Division of Neonatology, Pediatric Intensive Care & Neuropediatrics, Department of Pediatrics and Adolescent MedicineMedical University of ViennaViennaAustria
  13. 13.Division of Nephrology and Dialysis, Department of Medicine IIIMedical University of ViennaViennaAustria
  14. 14.Center for Congenital ImmunodeficienciesMedical University of Vienna & Jeffrey Modell Diagnostic and Research CenterViennaAustria

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