A novel frameshift variant in the ADA2 gene of a patient with a neurological phenotype: a case report

Background Adenosine deaminase 2 (ADA2) deficiency is an inherited autoinflammatory syndrome caused by a defect in the ADA2 gene. Most common manifestations include peripheral vasculopathy, early-onset stroke, immunodeficiency, and haematological manifestations. Patients with pathogenic variants that are more detrimental to ADA2’s enzymatic function (e.g. frameshift) have been reported to be prone to developing hematological phenotype. We report here the case of a 13-year-old Caucasian girl with a novel frameshift variant in the ADA2 gene and a clinical phenotype of early-onset stroke. Case presentation The patient was admitted to hospital with complaints of weakness in her right arm, unilateral facial weakness and speech problems. Her initial laboratory workup was normal; however, magnetic resonance imaging of her brain confirmed acute/subacute ischaemic changes in the posterior limb of the left-sided internal capsule and in the apical part of the thalamus. She also had manifestations of immunodeficiency – recurrent skin infections and otitis, chronic Molluscum contagiosum infection in anamnesis and B cell deficiency with a low level of serum IgA. The patient’s DNA was analysed and two pathogenic variants were identified in the ADA2 gene, confirming a diagnosis of adenosine deaminase 2 (ADA2) deficiency. While one of the variants (c.506G > A (p.Arg169Gln)) has been reported previously, the other one is a novel frameshift variant, namely, c.464del (p.Pro155Hisfs*29). The patient received stroke rehabilitation, which significantly improved her functional state. Tumour necrosis factor inhibitor and methotrexate treatment was commenced, and the patient has remained stable with no further ischaemic events. Conclusions Although rare, ADA2 deficiency should be considered in patients with early-onset stroke, especially with concomitant manifestations of inflammatory features or immunodeficiency. This case report extends the genotypic spectrum of ADA2 deficiency.