Background:
Autosomal recessive vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome (VIAHS) is a rare autosomal recessive disease caused by biallelic mutations in ADA2 (formerly known as Cat Eye Syndrome candidate region 1, or CECR1) [1-2]. The most prevalent mutation in the first reports of Adenosine deaminase deficiency (DADA2) was the p.Gly47Arg variant. However, more than 60 disease-causing variants, mostly missense single-nucleotide variants, and some splicing variants have now been described [3-4] across the entire coding region of ADA2 some of which are shown (Figure 1).
The ADA2 locus contains variability amongst humans, resulting in polymorphic variations associated with DADA2 [5]. The manifestation of VIAHS varies greatly amongst children and adults, including those homozygous for the same founder mutation, in the form of varying ages of presentation and variability of symptoms and severity [5-6]. Autoinflammatory characteristics constitute periodic fevers, musculoskeletal involvement, rashes (livedo racemosa/ reticularis) [4-7]. Vasculitis, usually manifested before ten years of age, appears as ischemic/hemorrhagic strokes or cutaneous polyarteritis nodosa (PAN), which remains a predominant feature in most cases described to date [7]. Dysregulation of immune response may manifest as autoimmunity, bone marrow deficiencies, and lymphadenopathy. Hematologic defects can include any cytopenias of a cell line defect to pancytopenias [4-7]. Gastrointestinal manifestations include hepatosplenomegaly, abdominal pain, and inflammatory bowel disease in up to 10% of patients. Other manifestations may include hypertension, hepatosplenomegaly, and neurological defects [7-8].
Here we report on a challenging diagnosis of VIAHS in a patient who presented at a very early age with a perianal abscess with fistula formation, fever, aphthous ulcers, bicytopenia, and hematochezia.