Diagnosis and management of Adenosine Deaminase 2 Deficiency children: the experience from China

Wang, Wei; Zhang, Tiannan; Zheng, Wei Xing; Zhong, Leilei; Wang, Lin; Li, Ji; Liu, Qian; Dong, Yujie; Song, Hongmei

doi:10.21203/rs.3.rs-60102/v2

Cited by 2 publications

(2 citation statements)

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“…Other rare clinical features, including growth retardation and complicated gastrointestinal ischemia, were reported in our cohort too. However, growth retardation, rigorously described in recent DADA reports, is found to impact a signi cant number (30%) of our patients [34]. Vasculitis manifestations of the gastrointestinal system generally include abdominal pain and, on rare occasions, intestinal necrosis with subsequent bowel perforation [12] Patient I, who presented with vasculitis phenotype, was noticed to have lower limb weakness that mimics transverse myelitis, which has not been previously described in children with DADA2.…”

Section: Discussionsupporting

confidence: 53%

Genotype and Phenotype of Adenosine Deaminase 2 Deficiency: The Experience From Saudi Arabia

Alabbas

Alanzi²,

Alrasheed³

et al. 2022

Preprint

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PurposeDADA2 is a rare and potentially fatal systemic autoinflammatory disease characterized by reduced or absence of ADA2 enzyme activity resulting from mutations in the ADA2 gene. Symptoms of DADA2 are variable and include vasculitis, immune dysregulation, and cytopenia. Scattered Saudi cases of DADA2 have been reported. We describe clinical, molecular, and outcome characterization of Saudi cases focused on phenotypic variability of DADA2.Methods To summarize the clinical features of Saudi patients with DADA2, we conducted a retrospective observational study in the seven major tertiary medical centers. Analysis of clinical characteristics, diagnostic findings, and treatment outcomes was obtained.ResultsWe identified 21 individuals with DADA2 from 14 families. At the time of the study, the patient's age was between 4 and 26 years (median age of 11.3 years). 20 patients presented during childhood. Homozygous c1447-1451del of ADA2 was the most frequently observed mutation in 38%, followed by c882-2A: G in 29%. Absent ADA2 activity was identified in all tested patients with homozygous mutations. Phenotypic manifestations included vasculopathy (stroke or cutaneous lesion) in 48%, cytopenia in 95%, autoinflammatory features such as intermittent fever, transaminases, and hepatosplenomegaly, and or immunodeficiency in 71% of the patients. 4 patients presented with Hodgkin lymphoma and one patient presented with clinical features mimic transverse myelitis, adding to the clinical spectrum of DADA2. Anti-tumor necrosis factor (anti-TNF) is the main treatment. However, regular blood transfusion, splenectomy, cyclosporine, and hematopoietic stem cell transplant (HSCT) were initiated in other patients because of anti-TNF failure. Morality was reported in 3 patients due to fulminant hepatitis and septic multi-organ failure.ConclusionOur cohort expands the variability of molecular and clinical characteristics of DADA2. Hematological phenotype predominates in the patients. Consensus diagnostic criteria are required to facilitate early diagnosis and initiation of prompt therapy. Evaluation of the rare disease complications such as cancer needs large prospective studies or disease registries

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Section: Discussionsupporting

confidence: 53%

Genotype and Phenotype of Adenosine Deaminase 2 Deficiency: The Experience From Saudi Arabia

Alabbas

Alanzi²,

Alrasheed³

et al. 2022

Preprint

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“…Consanguineous parents were noted in three families. 12 patients were reported before [30][31][32] , and the others were rst described in the cohort.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

A cohort study on deficiency of ADA2 from China

Han²,

Wu³

et al. 2022

Preprint

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Purpose: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function mutations in ADA2, characterized by systemic inflammation, vasculitis, immunodeficiency, and/or hematologic abnormalities. Methods: A retrospective analysis of patients with DADA2 diagnosed by whole exome sequencing at 17 rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype and treatment responses were analyzed.Results Thirty patients with DADA2 were enrolled in this cohort between January 2015 and December 2021. Median age at onset was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects in the cohort died from DADA2-related complications. The patients presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient with pure red cell aplasia (PRCA) and bone marrow failure (BMF) with variable cytopenia was observed in our cohort. Twenty-three (76.7%) patients received TNF inhibitors and all achieved clinical remission. Homozygous variants and compound heterozygous variants were identified in 5 and 25 patients, respective. Two patients received hematopoietic stem cell transplantation (HSCT), and both got remission. Among 39 unique variants in our cohort, six is novel.Conclusion: In order to establish the diagnosis early and prevent devastating clinical outcomes, genetic screening and/ or testing of adenosine deaminase enzymatic activity should be performed in patients with suspected clinical features. TNF inhibitors can be first line drug for patients with vasculitic DADA2. HSCT is an alternative choice for patients with refractory to TNF inhibitors or hematological disorders.

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Diagnosis and management of Adenosine Deaminase 2 Deficiency children: the experience from China

Cited by 2 publications

References 10 publications

Genotype and Phenotype of Adenosine Deaminase 2 Deficiency: The Experience From Saudi Arabia

Genotype and Phenotype of Adenosine Deaminase 2 Deficiency: The Experience From Saudi Arabia

A cohort study on deficiency of ADA2 from China

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