Asthma Allergy Immunology

Asthma Allergy Immunology

2023, Vol 21, Num, 2     (Pages: 143-149)

Different Phenotypes of a New Mutation: Two Siblings with ADA-2 Deficiency Presenting with Anemia and Neutropenia (Case Reports and Literature Review)

Oner OZDEMIR 1, Mehmet Fatih ORHAN 2, Mustafa BUYUKAVCI 2, Emine Aylin YILMAZ 3, Orhan GORUKMEZ 4,

1 Department of Pediatrics, Division of Allergy and Immunology, Research and Training Hospital of Sakarya University, Faculty of Medicine, Sakarya, Turkiye
2 Division of Hematology and Oncology, Research and Training Hospital of Sakarya University, Faculty of Medicine, Sakarya, Turkiye
3 Research and Training Hospital of Sakarya University, Faculty of Medicine, Sakarya, Turkiye
4 Department of Medical Genetics, Bursa City Hospital, Bursa, Turkiye

DOI: 10.21911/aai.102
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Deficiency of adenosine deaminase 2 (DADA2) is a childhood-onset disease known with pleiotropic clinical manifestations due to a monogenic form of systemic vasculopathy. Although the clinical spectrum of DADA2, linked to biallelic mutations in the ADA2 gene, has significantly expanded since 2014, approximately 200 cases have been reported thus far. In this report, two siblings are presented to draw attention to an unreported mutation of DADA2 and different phenotypic features of the same missense type homozygous mutation, p.Ser50Leu (c.149C>T). Next-generation sequencing demonstrated an autosomal recessive inherited missense type p.Ser50Leu (c.149C>T) variant homozygous mutation in the ADA-2 gene. The index patient is a 10-year-old Iraqi citizen boy who was referred to us with a complaint of anemia. The patient still needed blood transfusions after 2 hematopoietic stem cell transplantations. His older brother was an 11-year-old boy who presented to the emergency with a history of recurrent lung infections since 7 years of age. Considering the genotype-phenotype relationship from literature data, although vasculitis and low ADA2 activity are defined in cases with missense mutations, immuno-hematological manifestations are remarkable in our patients rather than vasculitic manifestations. While bone marrow failure findings e.g., anemia, neutropenia, etc. are reported to be seen in the 5th and 6th decades of life, those were predominant clinical features in our patients despite their younger age. DADA2 should also be kept in mind in cases of otherwise unexplained cytopenia, especially when associated with panhypogammaglobulinaemia and bone marrow hypocellularity, irrespective of the age of the patient at presentation.

Keywords : Deficiency of adenosine deaminase 2, anemia, neutropenia, livedo racemosa, hypogammaglobulinemia