ADA2 deficiency (DADA2) misdiagnosed as systemic onset juvenile idiopathic arthritis in a child carrying a novel compound heterozygous ADA2 mutation: a case report

Abstract

Background: The deficiency of adenosine deaminase 2 (DADA2) is caused by an autosomal recessive bi-allelic loss-of-function mutation in the adenosine deaminase 2 (ADA2) gene. DADA2 is a monogenic inherited autoinflammatory disorder characterized by early-onset vasculopathy for which the symptoms range from skin lesions to very severe multiorgan involvement, including life-threatening ischemia and/or hemorrhagic strokes. Owing to the diversity of clinical presentation and the absence of suggestive features, differentiating DADA2 from other inflammatory disorders in the early stages of disease presentation is difficult. Here, we describe the case of a 3-year-old boy who had been misdiagnosed for nearly 2 years before he was definitively diagnosed with DADA2.Case Description: A previously healthy 3-year-old boy was initially diagnosed with systemic onset juvenile idiopathic arthritis (soJIA) owing to recurrent unprovoked fever and elevated acute phase reactants.He developed intractable hypertension during treatment, which his doctor considered an adverse drug reaction. Monogenic inherited autoinflammatory disorders were not suspected until the patient developed intestinal perforation and ensuing recurrent abdominal pain that coincided with fever. Gene sequence analysis revealed a novel compound heterozygous mutation in ADA2. The ADA2 enzyme activity was almost completely lost in the patient. Conclusions:The broad phenotypic spectrum of DADA2 makes early diagnosis challenging. DADA2 should be considered in case of early-onset vasculitis, which is the most common phenotype of DADA2.Early identification and treatment will result in significant improvement of the disease.

Central retinal artery occlusion in a child with ADA2 deficiency: A case report

“…it improves the overall clinical manifestations, control fever episodes and vasculopathy, and prevent strokes in patients with ADA2 deficiency syndrome. Although steroids and other immunosuppressive drugs can be used, they are thought not to prevent strokes 14 . In this case, the disease was well controlled on Adalimumab.…”

A case report on deficiency of adenosine deaminase 2 with relapse–remission course and analysis of genotype–phenotype correlation

“…Patients with DADA2 may present with a range of clinical phenotypes, including recurrent fever, livedo racemosa, ischemic strokes, and hematological abnormalities (Caorsi et al, 2017; Li et al, 2023; Navon Elkan et al, 2014; Zhou et al, 2014). The wide range of disease phenotypes can cause patients to be easily misdiagnosed (Springer et al, 2018; Yin et al, 2023). A recent study estimated a DADA2 prevalence of 1 in 222,164 individuals worldwide, and more than 30,000 DADA2 cases are predicted among the world's population of 7.7 billion (Jee et al, 2022).…”

Novel pathogenic ADA2 mutations: alert to diagnosis challenge of ADA2 deficiency

“…In a recent study published on Translational Paediatrics , Yin and colleagues ( 15 ) reported a 3-year-old boy with DADA2 who initially presented with nonspecific clinical manifestations including recurrent fever, mildly enlarged lymph nodes, and elevated acute phase reactants, with an initial diagnosis of systemic onset juvenile idiopathic arthritis. The key events leading to a re-evaluation of the initial diagnosis were the presence of intractable hypertension and gastrointestinal complications suspicious for underlying vasculopathy, and an unsustained response to immunosuppressive treatments.…”

“…Study of Yin et al , which was published on Translational Paediatrics , identified a novel compound heterozygous mutation in ADA2 gene ( 15 ), c.737 G>C (p. Arg246Thr) located in exon 3 and c.827 T>C (p.Phe276Ser) located in exon 4. Their experimental data revealed ADA2 enzyme activity was almost completely lost in this patient.…”