The deficiency of adenosine deaminase 2 (DADA2) is an inborn immunity error caused by loss-of-function mutations in the ADA2 gene. Manifestations include vasculopathy and immunological and hematological abnormalities. It is unknown how ADA2 loss causes bone marrow (BM) failure, and understanding these mechanisms is essential for developing new targeted therapies.
A 31-year-old man was admitted to our hospital with suspicion of myelofibrosis and myelodysplastic syndrome, with unclear etiology.
His records include the product of a twin pregnancy; since his early infancy, he has presented with recurrent oral ulcers and denies any other symptoms.
At 29, in a routine assessment for an orthopedic surgery, tricytopenia was found.
At 30, his clinical condition got worse, and he started to need blood transfusions weekly. Myelofibrosis was suspected but did not fulfill the criteria. His hematological assessment included CBC and differentials: Hb 10.7 mg/dl, GBC 2,830/mm3 (neutrophils 70%, lymphocytes 17%, monocytes 13%, eosinophils 0%, and B 0%), Plat 92.000/mm3, BM biopsy that showed altered CD4/CD8, with development arrest, and infiltration of CD8+ T cells. Molecular evaluation: Jak2 V617f, Gata1, Gata2, Tet2, and CALR were negative. Immunological workup: he presented with mild hypogammaglobulinemia; vaccine responses: good response to the tetanus vaccine but no response to the polysaccharide pneumococcal vaccine. Flow cytometry assays showed that T cells were normal, NK decreased, and B cells and memory B cells were low.
At physical examination, he presented warts on both hands and a geographic tongue with leukoplakia and peripheral edema.
An inborn error of immunity was highly suspected. WES: A missense pathogenic variant in ADA2 (missense, variant ID: 22-17207107-C-T) was found. Measurement of plasma ADA2 enzymatic activity was deficient. DADA2 was diagnosed.
The patient is under anti-TNF treatment and Ig replacement therapy and is being evaluated for a BM transplant.
