Deficiency of Adenosine Deaminase 2 (DADA2): One Disease, Several Faces

Chavan, Pallavi Pimpale; Ramadoss, Divya; Khan, Archana; Lee, Pui Y.; Khubchandani, Raju

doi:10.1007/s12098-021-03809-2

Cited by 6 publications

(10 citation statements)

References 3 publications

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“…The patient in our case report belonged to the Agarwal community of India and had a p.Gly47Arg mutation. In two of the published case series on DADA2 patients in India, the most common mutation was p.Gly47Arg, and most people having this mutation did, in fact, belong to the Agarwal community, mirroring our case presentation [19,20].…”

Section: Discussionsupporting

confidence: 67%

A Rare Genetic Mutation Leading to a Deficiency of Adenosine Deaminase 2 Enzyme in a Long-Standing Case of Cutaneous Polyarteritis Nodosa: A Case Report

Contractor¹,

Bhavsar²,

Joshi³

et al. 2022

Cureus

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Vasculitis is an inflammatory disorder of blood vessels affecting multiple organs. A deficiency of adenosine deaminase enzyme type 2 (DADA2) is a novel condition identified as a monogenic cause of cutaneous vasculitis. Since its first description in 2014, numerous case series and literature across several countries have expanded the scope of our understanding of this rare genetic condition. However, due to a scarcity of reported cases in adults, little is known regarding its full spectrum of clinical presentations, treatment guidelines, or outcomes in the adult patient population. It is established that it commonly affects multiple organ systems, such as the skin, musculoskeletal, neurological, hematological, gastrointestinal, and renal systems. It presents with a wide range of clinical manifestations, including fever, Livedoid rash, cutaneous polyarteritis nodosa, polyneuropathy, and immunodeficiency. Such a varied clinical spectrum opens an opportunity for discussion to list some of the differential signs of DADA2. In this article, we report a unique case of a 26-year-old male with a delay of nine years in diagnosing a genetic mutation that led to DADA2. In addition, a 10-year history of recurring cutaneous ulcers and peripheral neuropathy makes this case a noteworthy addition to the literature on cutaneous vasculitis and its miscellaneous causes.

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Section: Discussionsupporting

confidence: 67%

A Rare Genetic Mutation Leading to a Deficiency of Adenosine Deaminase 2 Enzyme in a Long-Standing Case of Cutaneous Polyarteritis Nodosa: A Case Report

Contractor¹,

Bhavsar²,

Joshi³

et al. 2022

Cureus

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“…Anaemia was reported in 97 patients (25.6%), of whom 4 showed a Blackfan-Diamond Anaemia and 23 Pure Red Aplasia [ 1 , 2 , 4 , 7 – 9 , 11 , 12 , 15 – 18 , 20 , 21 , 29 , 31 , 33 , 36 , 40 , 43 , 47 – 49 , 53 , 58 , 59 , 62 , 63 , 65 – 67 , 71 , 76 , 77 , 82 , 83 , 86 – 89 ]. Thrombocytopenia was described in 34 patients (8.9%) [ 1 , 4 , 8 , 9 , 11 , 12 , 15 , 17 , 18 , 21 , 36 , 40 , 42 , 49 , 60 , 65 , 67 , 83 ], neutropenia in 76 (20.1%) [ 1 , 4 , 8 , 9 , 11 , 12 , 15 , 17 , 18 , 21 , 22 , 32 , 36 , 38 , 42 , 43 , 45 , ...…”

Section: Resultsmentioning

confidence: 99%

“…Splenomegaly was found in 116 patients (30.6%) [ 1 , 4 , 7 – 9 , 12 , 15 – 18 , 22 , 30 , 31 , 35 , 36 , 38 – 40 , 58 , 62 – 66 , 68 , 71 , 74 , 77 – 79 , 81 , 83 , 85 – 88 , 90 , 91 ], hepatomegaly in 89 (23.5%) [ 1 , 4 , 8 , 9 , 12 , 17 , 18 , 27 , 28 , 30 , 31 , 36 , 49 , 54 , 58 , 62 – 66 , 71 , 74 , 78 , 81 , 83 , 87 , 90 , 91 ], and diffuse lymphadenopathies in 27 (7.14%) [ 1 , 4 , 9 , 12 , 17 , 18 , 27 , 30 , 54 , 58 , 62 , 65 , 71 , 86 , 90 ].…”

Section: Resultsmentioning

confidence: 99%

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A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review

Maccora

Maniscalco

Campani

et al. 2023

Orphanet J Rare Dis

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Introduction Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally described as mimicker of polyarteritis nodosa, with immunodeficiency and early-onset stroke. Methods A systematic review according to PRISMA approach, including all articles published before the 31st of August 2021 in Pubmed and EMBASE database was performed. Results The search identified 90 publications describing 378 unique patients (55.8% male). To date 95unique mutations have been reported. The mean age at disease onset was 92.15 months (range 0–720 months), 32 (8.5%) showed an onset of the first signs/symptoms after 18 years old and 96 (25.4%) after 10 years old. The most frequent clinical characteristics described were cutaneous (67.9%), haematological manifestations (56.3%), recurrent fever (51.3%), neurological as stroke and polyneuropathy (51%), immunological abnormalities (42.3%), arthralgia/arthritis (35.4%), splenomegaly (30.6%), abdominal involvement (29.8%), hepatomegaly (23.5%), recurrent infections (18.5%), myalgia (17.9%), kidney involvement (17.7%) etc. Patients with skin manifestations were older than the others (101.1 months SD ± 116.5, vs. 75.3 SD ± 88.2, p 0.041), while those with a haematological involvement (64.1 months SD ± 75.6 vs. 133.1 SD ± 133.1, p < 0.001) and immunological involvement (73.03 months SD ± 96.9 vs. 103.2 SD ± 112.9, p 0.05) are younger than the others. We observed different correlations among the different clinical manifestations. The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) has improved the current history of the disease. Conclusion Due to this highly variable phenotype and age of presentation, patients with DADA2 may present to several type of specialists. Given the important morbidity and mortality, early diagnosis and treatment are mandatory.

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“…Hypertension and gastrointestinal symptoms are all vasculopathy-related manifestations. Angiography in some patients has revealed stenosis and/or aneurysms of abdominal arteries, particularly the mesenteric, celiac, and renal arteries, and the intestinal histopathology has revealed necrotizing vasculitis ( 1 , 2 , 12 ). However, the CT angiography examination of our patient did not reveal any aneurysm or arterial stenosis, possibly because the vessels involved in DADA2 were small, and CT and MRA are not always sensitive enough to identify such affected vessels.…”

Section: Discussionmentioning

confidence: 99%

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

Yin¹,

Fan²,

Ma³

et al. 2023

Transl Pediatr

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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.

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Deficiency of Adenosine Deaminase 2 (DADA2): One Disease, Several Faces

Cited by 6 publications

References 3 publications

A Rare Genetic Mutation Leading to a Deficiency of Adenosine Deaminase 2 Enzyme in a Long-Standing Case of Cutaneous Polyarteritis Nodosa: A Case Report

A Rare Genetic Mutation Leading to a Deficiency of Adenosine Deaminase 2 Enzyme in a Long-Standing Case of Cutaneous Polyarteritis Nodosa: A Case Report

A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review

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

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