Abstract
Describe the clinical characteristics and histopathology findings in a family with two siblings affected with deficiency of adenosine deaminase 2 (DADA2). Both patients presented in childhood with polyarthritis and developed significant neurological and gastrointestinal features of DADA2 in ear, including variable degrees of immunologic and hematologic manifestations. Adenosine Deaminase 2 (ADA2; also known as cat eye syndrome chromosome region, candidate 1 gene; CECR1) exon sequencing and serum ADA2 levels were performed to confirm the diagnosis of DADA2. Comparison of serum adenosine deaminase 2 levels was made to DADA2 patients, carriers, and healthy controls in Patient 2. Autopsy specimens from brain and liver tissues were submitted for analysis. Both patients were found to carry a previously reported rare intronic missense mutation predicted to affect the transcript splicing (c.973-2A > G; rs139750129) and an unreported missense mutation p.Val458Asp (c.1373T > A; V458D). Both brothers started therapy with a tumor necrosis factor inhibitor following the molecular diagnosis of DADA2 with good response and were eventually tapered off prednisone. However, Patient 1 died 18 months later due to complications of end-stage liver disease. His autopsy showed evidence for nodular hyperplasia of the liver often seen in common variable immunodeficiency (CVID) and numerous small, old infarcts throughout the brain that had not been demonstrated on prior MRI/MRA imaging. These cases emphasize the importance of recognition of DADA2 in adults, compare CNS imaging modalities to pathologic findings and suggest similarities in liver pathology between DADA2 and CVID. MRI may not be most sensitive method to identify small subcortical infarcts in patients suspected to have DADA2.
Highlights
Deficiency of adenosine deaminase 2 (DADA2) is a recently described monogenic autoinflammatory disease that can mimic polyarteritis nodosa (PAN)
One of the hallmark clinical features of DADA2 is early-onset, recurrent strokes with the vast majority occurring in early childhood [1]
There are several case reports of intracerebral hemorrhage in DADA2, most patients present with ischemic strokes
Summary
Deficiency of adenosine deaminase 2 (DADA2) is a recently described monogenic autoinflammatory disease that can mimic polyarteritis nodosa (PAN). A 40-year-old Caucasian male, with a prior diagnosis of PAN, presented in January 2016 with large volume hematemesis from esophageal varices related to portal hypertension. Throughout his childhood he had chronic arthralgia and swelling of his ankles diagnosed as juvenile idiopathic arthritis. He developed recurrent violaceous subcutaneous lesions that would ulcerate, but were responsive to glucocorticoids He was diagnosed with PAN based on skin biopsies. He required a longterm maintenance dose of prednisone 7.5 mg daily, as reduction would led to recurrent skin lesions In childhood, he developed poorly explained visual loss without evidence of inflammatory eye disease on physical exam. Adenosine deaminase 2 levels were tested only in Patient 2 with comparisons made to DADA2 patients, adult carriers for ADA2 mutations and adult healthy controls
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