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.