The same mutation in a family with adenosine deaminase 2 deficiency

Sözeri, Betül; Ercan, Gozde; Doğan, Özlem Akgün; Yildiz, Jale; Demir, Ferhat; Doğanay, Levent

doi:10.1007/s00296-019-04444-z

Cited by 12 publications

(10 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Deficiency of ADA2 arises from mutations affecting catalytic activity, protein dimerization, and secretion of ADA2 and causes vasculopathy and inflammation in many organs and/or hemorrhagic stroke (Navon Elkan et al, 2014;Zhou et al, 2014;Meyts and Aksentijevich, 2018;Gibson et al, 2019;Sahin et al, 2020;Zervou et al, 2020;Sozeri et al, 2021). Less frequent neurological manifestations include spastic diplegia or paraplegia, peripheral polyneuropathy, ataxia, neurosensory deafness, and cerebral atrophy (Meyts and Aksentijevich, 2018).…”

Section: Adenosine Deaminasementioning

confidence: 99%

Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

View full text Add to dashboard Cite

Adenosine, acting both through G-protein coupled adenosine receptors and intracellularly, plays a complex role in multiple physiological and pathophysiological processes by modulating neuronal plasticity, astrocytic activity, learning and memory, motor function, feeding, control of sleep and aging. Adenosine is involved in stroke, epilepsy and neurodegenerative pathologies. Extracellular concentration of adenosine in the brain is tightly regulated. Adenosine may be generated intracellularly in the central nervous system from degradation of AMP or from the hydrolysis of S-adenosyl homocysteine, and then exit via bi-directional nucleoside transporters, or extracellularly by the metabolism of released nucleotides. Inactivation of extracellular adenosine occurs by transport into neurons or neighboring cells, followed by either phosphorylation to AMP by adenosine kinase or deamination to inosine by adenosine deaminase. Modulation of the nucleoside transporters or of the enzymatic activities involved in the metabolism of adenosine, by affecting the levels of this nucleoside and the activity of adenosine receptors, could have a role in the onset or the development of central nervous system disorders, and can also be target of drugs for their treatment. In this review, we focus on the contribution of 5′-nucleotidases, adenosine kinase, adenosine deaminase, AMP deaminase, AMP-activated protein kinase and nucleoside transporters in epilepsy, cognition, and neurodegenerative diseases with a particular attention on amyotrophic lateral sclerosis and Huntington’s disease. We include several examples of the involvement of components of the adenosine metabolism in learning and of the possible use of modulators of enzymes involved in adenosine metabolism or nucleoside transporters in the amelioration of cognition deficits.

show abstract

Section: Adenosine Deaminasementioning

confidence: 99%

Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Skin manifestations, of note panarteritis nodosa-like lesions, have been reported from the first descriptions [ 1 , 2 ]. Among the 257 patients with a cutaneous involvement, 180 showed a livedo reticularis or livedo racemose (47.1% of all DADA2 patients) [ 1 , 2 , 4 , 9 , 11 , 12 , 15 , 16 , 22 , 23 , 25 , 26 , 28 – 31 , 34 , 36 , 37 , 40 , 43 , 44 , 46 – 48 , 50 , 52 , 53 , 56 , 59 , 60 , 62 – 64 , 66 , 67 , 69 – 76 , 81 – 83 , 87 , 90 , 91 ], 89 panarteritis nodosa-like lesions (23.5%) [ 1 , 2 , 5 , 9 , 12 , 20 , 21 , 23 , 25 , 26 , 28 , 30 , 31 , 34 , 35 , 38 , 40 , 43 , 44 , 52 , 53 , 60 , 64 , 66 , 69 , 71 …”

Section: Resultsmentioning

confidence: 99%

“…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%

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

View full text Add to dashboard Cite

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.

show abstract

“…DADA2 is increasingly being recognized as a monogenic etiology for PAN with systemic inflammation and vasculitis features and biallelic variants in ADA2 have been identified in ~ 25-31% of childhood PAN cases [1,2,8,11,21,26,28,[38][39][40][41][42]. Genetic testing and/or ADA2 activity detection should be considered in all patients with recurrent fever accompanied unexplained elevated CRP and/or ESR, especially in those with livedo racemosa/reticularis and evidence of PAN-like vasculitis.…”

Section: Discussionmentioning

confidence: 99%

A Cohort Study on Deficiency of ADA2 from China

Han

et al. 2023

J Clin Immunol

View full text Add to dashboard Cite

Purpose Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. Methods A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. Results Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. Conclusion To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

show abstract

The same mutation in a family with adenosine deaminase 2 deficiency

Cited by 12 publications

References 24 publications

Metabolic Aspects of Adenosine Functions in the Brain

Metabolic Aspects of Adenosine Functions in the Brain

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

A Cohort Study on Deficiency of ADA2 from China

Contact Info

Product

Resources

About