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

IntroductionDeficiency 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.MethodsA systematic review according to PRISMA approach, including all articles published before the 31st of August 2021 in Pubmed and EMBASE database was performed.ResultsThe 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-TNF alpha and hematopoietic cell stems transplantation (HCST) has improved the current history of the disease.ConclusionDue 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.

Automated summary

Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease with a highly variable phenotype. A systematic review identified 90 publications describing 378 patients with DADA2. The most common clinical characteristics included cutaneous manifestations, hematological manifestations, recurrent fever, stroke and polyneuropathy, immunological abnormalities, arthralgia/arthritis, splenomegaly, abdominal involvement, hepatomegaly, recurrent infections, myalgia, and kidney involvement. Early diagnosis and treatment are crucial due to the significant morbidity and mortality associated with this disease.