scholarly journals A Novel Germline Mutation of ADA2 Gene in Two “Discordant” Homozygous Female Twins Affected by Adenosine Deaminase 2 Deficiency: Description of the Bone-Related Phenotype

2021 ◽  
Vol 22 (15) ◽  
pp. 8331
Author(s):  
Silvia Vai ◽  
Erika Marin ◽  
Roberta Cosso ◽  
Francesco Saettini ◽  
Sonia Bonanomi ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Systemic Vasculitis ◽  
Systemic Disease ◽  
Loss Of Function ◽  
Mineral Density ◽  
Skeletal Health ◽  
Related Phenotype ◽  
Adenosine Deaminase 2

Adenosine Deaminase 2 Deficiency (DADA2) syndrome is a rare monogenic disorder prevalently linked to recessive inherited loss of function mutations in the ADA2/CECR1 gene. It consists of an immune systemic disease including autoinflammatory vasculopathies, with a frequent onset at infancy/early childhood age. DADA2 syndrome encompasses pleiotropic manifestations such as stroke, systemic vasculitis, hematologic alterations, and immunodeficiency. Although skeletal abnormalities have been reported in patients with this disease, clear information about skeletal health, with appropriate biochemical-clinical characterization/management, its evolution over time and any appropriate clinical management is still insufficient. In this paper, after a general introduction shortly reviewing the pathophysiology of Ada2 enzymatic protein, its potential role in bone health, we describe a case study of two 27 year-old DADA2 monozygotic female twins exhibiting bone mineral density and bone turnover rate abnormalities over the years of their clinical follow-up.

scholarly journals Deficiency of adenosine deaminase 2 triggers adenosine-mediated NETosis and TNF production in patients with DADA2

Blood ◽  
2019 ◽  
Vol 134 (4) ◽  
pp. 395-406 ◽  
Author(s):  
Carmelo Carmona-Rivera ◽  
Sami S. Khaznadar ◽  
Kyawt W. Shwin ◽  
Jorge A. Irizarry-Caro ◽  
Liam J. O’Neil ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Systemic Vasculitis ◽  
Remission Induction ◽  
Loss Of Function ◽  
Pathogenic Role ◽  
Study Objective ◽  
Adenosine Deaminase 2

Abstract Reduction of adenosine deaminase 2 (ADA2) activity due to autosomal-recessive loss-of-function mutations in the ADA2 gene (previously known as CECR1) results in a systemic vasculitis known as deficiency of ADA2 (DADA2). Neutrophils and a subset of neutrophils known as low-density granulocytes (LDGs) have been implicated in the pathogenesis of vasculitis, at least in part, through the formation of neutrophil extracellular traps (NETs). The study objective was to determine whether neutrophils and NETs play a pathogenic role in DADA2. In vivo evidence demonstrated NETs and macrophages in affected gastrointestinal tissue from patients with DADA2. An abundance of circulating LDGs prone to spontaneous NET formation was observed during active disease in DADA2 and were significantly reduced after remission induction by anti–tumor necrosis factor (TNF) therapy. Increased circulating LDGs were identified in unaffected family members with monoallelic ADA2 mutations. Adenosine triggered NET formation, particularly in neutrophils from female patients, by engaging A1 and A3 adenosine receptors (ARs) and through reactive oxygen species– and peptidylarginine deiminase–dependent pathways. Adenosine-induced NET formation was inhibited by recombinant ADA2, A1/A3 AR antagonists, or by an A2A agonist. M1 macrophages incubated with NETs derived from patients with DADA2 released significantly greater amounts of TNF-α. Treatment with an A2AAR agonist decreased nuclear translocation of NF-κB and subsequent production of inflammatory cytokines in DADA2 monocyte-derived macrophages. These results suggest that neutrophils may play a pathogenic role in DADA2. Modulation of adenosine-mediated NET formation may contribute a novel and directed therapeutic approach in the treatment of DADA2 and potentially other inflammatory diseases.

scholarly journals Novel Adenosine Deaminase 2 (ADA2) Mutations Associated With Hematological Manifestations

2021 ◽  
Vol 9 ◽  
pp. 232470962110567
Author(s):  
Reem Albalawi ◽  
Ehab Hanafy ◽  
Haifa Alnafea ◽  
Mohammed Altowijiry ◽  
Shaima Riyad ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Gene Mutations ◽  
Pure Red Cell Aplasia ◽  
Autoinflammatory Disorder ◽  
Hematological Disorders ◽  
Laboratory Techniques ◽  
First Case ◽  
Adenosine Deaminase 2 ◽  
Hematological Manifestations

Recent progress in laboratory techniques, particularly, identification of novel disease-causing genes, has led to the detection of different gene mutations that might be implicated in the pathogenesis of different hematological disorders like pure red cell aplasia (PRCA) and neutropenia. An autoinflammatory disorder known as deficiency of adenosine deaminase 2 (DADA2) has been recently noticed to present with variable hematologic abnormalities. We report 2 patients who presented with hematologic abnormalities in which 2 ADA2 gene mutations were detected. The first case is a 5-year-old girl who presented with severe PRCA and autoimmune hemolytic anemia without any other manifestation of DADA2 that resulted from a novel CECR1 c.714_738dup, p. (Ala247Glnfs*16) homozygous variant. The second case is a 10-year-old boy, known to have Hodgkin lymphoma and was under follow-up for 6 years; he presented with persistent neutropenia and was discovered to be homozygous for ADA2 c.1447_1451del, p. (Ser483Profs*5). In conclusion, we report two different novels ADA2 variants in two children; the first presented with PRCA and the second presented with persistent neutropenia. This report aims to raise the concerns regarding the use of genetic testing in different hematologic diseases with indefinite etiology, as it will lead to the best therapeutic strategies without the need for unnecessary interventions.

scholarly journals OR13-001 Loss-of-function mutations in CECR1, encoding adenosine deaminase 2 (ADA2), cause recurrent fevers and early onset strokes

2013 ◽  
Vol 11 (Suppl 1) ◽  
pp. A263
Author(s):  
Q Zhou ◽  
A Zavialov ◽  
J Chae ◽  
M Hershfield ◽  
R Sood ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Early Onset ◽  
Loss Of Function ◽  
Adenosine Deaminase 2

scholarly journals Evaluation and Management of Skeletal Health in Celiac Disease: Position Statement

2012 ◽  
Vol 26 (11) ◽  
pp. 819-829 ◽  
Author(s):  
Mona A Fouda ◽  
Aliya A Khan ◽  
Muhammad Sultan ◽  
Lorena P Rios ◽  
Karen McAssey ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Position Statement ◽  
Current Evidence ◽  
Mineral Density ◽  
High Fracture ◽  
Skeletal Health ◽  
X Ray ◽  
Increased Risk ◽  
One Year

OBJECTIVE: To review the evaluation and management of skeletal health in patients with celiac disease (CD), and to make recommendations on screening, diagnosis, treatment and follow-up of low bone mineral density (BMD) in CD patients.METHODS: A multidisciplinary team developed clinically relevant questions for review. An electronic search of the literature was conducted using the MEDLINE and EMBASE databases from 1996 to 2010. All original studies, reviews and guidelines, both pediatric and adult, were included. A document summarizing the results of the review and proposed recommendations was prepared and underwent multiple revisions until consensus was reached.RESULTS: At diagnosis, approximately one-third of adult CD patients have osteoporosis, one-third have osteopenia and one-third have normal BMD. Children with CD have low bone mass at diagnosis. Adult and pediatric CD patients are at increased risk of fractures.DISCUSSION: For adults, serum calcium, albumin, 25(OH) vitamin D3, parathyroid hormone and 24 h urine calcium testing should be performed at diagnosis; patients with ‘classic’ CD and those at risk for osteoporosis should undergo a dual x-ray absorptiometry scan. An abnormal baseline dual x-ray absorptiometry scan should be repeated one to two years after initiation of a gluten-free diet (GFD). For children, BMD should be assessed one year after diagnosis if GFD adherence is not strict. A GFD is the most important treatment for bone loss. Supplemental antiresorptives may be justified in those who remain at high fracture risk (eg, postmenopausal women, older men) after implementation of a GFD.CONCLUSION: Current evidence does not support the screening of all CD patients for low BMD at diagnosis. Follow-up BMD assessment should be performed one to two years after initiation of a GFD.

scholarly journals Adenosine Deaminase 2 Deficiency: Its pleiotropic manifestations may also affect bone metabolism? A case study on two homozygous female twins

Bone Reports ◽  
2021 ◽  
Vol 14 ◽  
pp. 101021
Author(s):  
Erika Marin ◽  
Iacopo Chiodini ◽  
Luca Persani ◽  
Alberto Falchetti ◽  
Silvia Vai
Keyword(s):  
Bone Metabolism ◽  
Adenosine Deaminase ◽  
Adenosine Deaminase 2 ◽  
Affect Bone Metabolism

scholarly journals Clinical follow-up on a cohort of patients with deficiency of adenosine deaminase 2 (DADA2)

2015 ◽  
Vol 13 (S1) ◽  
Author(s):  
K Barron ◽  
A Ombrello ◽  
D Stone ◽  
P Hoffmann ◽  
I Aksentijevich ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Adenosine Deaminase 2

Adenosine deaminase 2 deficiency presenting as spastic paraplegia and systemic vasculitis

2016 ◽  
Vol 263 (4) ◽  
pp. 818-820 ◽  
Author(s):  
Fabiano de Oliveira Poswar ◽  
Raymundo Mesko Tomkowski da Fonseca ◽  
Leonardo Cordenonzi Pedroso de Albuquerque ◽  
Qing Zhou ◽  
Laura Bannach Jardim ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Systemic Vasculitis ◽  
Spastic Paraplegia ◽  
Adenosine Deaminase 2

scholarly journals Therapeutical Approach of Osteoporosis — a Multidisciplinary Issue

2013 ◽  
Vol 59 (4) ◽  
pp. 226-230
Author(s):  
Gliga Camelia ◽  
Marcu Simona ◽  
Gliga M
Keyword(s):  
Preventive Measures ◽  
Systemic Disease ◽  
Hormone Replacement ◽  
Bone Fragility ◽  
Mineral Density ◽  
Treatment Of Osteoporosis ◽  
X Ray ◽  
Different Types ◽  
Laboratory Investigations

AbstractOsteoporosis is the most frequent systemic disease of the bone, that affects elderly, mainly women in menopause. It can be defined by lowering of bone mass and microarchitectural deterioration of the bone tissue, resulting in an increased bone fragility. Main complications of osteoporosis are fractures of the vertebrae, hips and forearm. In view of its large variety of causes and manifestations, diagnostic and therapeutical approach in osteoporosis represents a multidisciplinary issue. The accurate diagnosis of osteoporosis is based on a method that measures the bone mineral density, expressed by the T-score, using dual energy X-ray absorptiometry, so called DXA. Lately, in practice in order for establishing the risk of osteoporosis and osteoporotic fracture the FRAX tool is increasingly used (The Fracture Risk Assessment). Treatment of osteoporosis is complex involving non-pharmacological and pharmacological measures. Non-pharmacological methods include preventive measures like exercise, external hip protectors, increase of dietary intake of calcium, vitamin D and proteins, especially in elderly, over 65 years. Pharmacological measures are represented by different types of drugs, including biphosphonates, bone formation stimulatory drugs, agents with new mechanisms of action, hormone replacement therapy and they will be indicated only after a detailed clinical and paraclinical examination of the patient. Regardless of the chosen pharmacological measure, periodical follow-up of efficacy, side-effects and complications of antiosteoporotic treatment, by clinical examination and laboratory investigations targeting bone remodelling, is strongly indicated.

scholarly journals A Case of Deficiency of Adenosine Deaminase 2: 28 years of Diagnostic Challenges

2021 ◽  
pp. 340-347
Author(s):  
Clara Pardinhas ◽  
Gustavo Santo ◽  
Luís Escada ◽  
Jorge Rodrigues ◽  
Maria Rosário Almeida ◽  
...  
Keyword(s):  
Renal Insufficiency ◽  
Adenosine Deaminase ◽  
Autosomal Recessive ◽  
Autoinflammatory Disease ◽  
Clinical Manifestations ◽  
Loss Of Function ◽  
Childhood Onset ◽  
Amyloid A ◽  
Inflammatory State ◽  
Adenosine Deaminase 2

Deficiency of adenosine deaminase 2 (DADA2) is a unique monogenic autoinflammatory disease caused by autosomal recessive loss-of-function mutations in the CECR1 gene which presents as childhood-onset small- and medium-vessel vasculitis. Previously, many of these patients were misdiagnosed and thought to have clinical features of systemic polyarteritis nodosum, which negatively influenced its outcome, since TNF inhibitors seem to have efficacy on the vasculitic phenotype of DADA2. We present a case of a 28-year-old woman with a lifelong unknown syndrome and unique clinical manifestations recently recognized as DADA2. The first manifestation, at 3 months of age, was an episode of facial paralysis during which renovascular hypertension was diagnosed. Later, she developed episodes of prolonged fever, polyarthritis, Raynaud’s phenomenon, gastrointestinal bleeding, and intracerebral hemorrhage. This inflammatory state ultimately led to the development of amyloid A amyloidosis and renal insufficiency.

Intensive Stuttering Therapy With Telepractice Follow-up: A Case Study

2011 ◽  
Vol 21 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Farzan Irani ◽  
Rodney Gabel
Keyword(s):  
Case Report ◽  
Therapeutic Intervention ◽  
Intensive Therapy ◽  
Positive Outcome ◽  
Eclectic Approach

This case report describes the positive outcome of a therapeutic intervention that integrated an intensive, residential component with follow-up telepractice for a 21 year old male who stutters. This therapy utilized an eclectic approach to intensive therapy in conjunction with a 12-month follow-up via video telepractice. The results indicated that the client benefited from the program as demonstrated by a reduction in percent stuttered syllables, a reduction in stuttering severity, and a change in attitudes and feelings related to stuttering and speaking.

Sign in / Sign up

Export Citation Format

Share Document