Stroke as Initial Manifestation of Adenosine Deaminase 2 Deficiency

Elbracht, Miriam; Mull, Michael; Wagner, Norbert; Kuhl, Christiane K.; Schöser, Benedikt; Kurth, Ingo; Tenbrock, Klaus; Häusler, Martin

doi:10.1055/s-0036-1597611

Cited by 23 publications

(17 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several case series reported arterial hypertension, renal vessel artery aneurysm, renal artery stenosis, kidney inflammation with dense lymphocytic infiltration, and glomerular scarring [ 1 , 2 , 49 ]. GI manifestations include abdominal pain and inflammatory bowel disease in up to 10% of patients [ 1 , 41 , 44 , 45 , 66 , 67 ]. Pathology report showed a CVID-like inflammatory bowel phenotype with absent plasma cells [ 7 ].…”

Section: Clinical Presentationmentioning

confidence: 99%

Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment

2018

View full text Add to dashboard Cite

Deficiency of ADA2 (DADA2) is the first molecularly described monogenic vasculitis syndrome. DADA2 is caused by biallelic hypomorphic mutations in the ADA2 gene that encodes the adenosine deaminase 2 (ADA2) protein. Over 60 disease-associated mutations have been identified in all domains of ADA2 affecting the catalytic activity, protein dimerization, and secretion. Vasculopathy ranging from livedo reticularis to polyarteritis nodosa (PAN) and life-threatening ischemic and/or hemorrhagic stroke dominate the clinical features of DADA2. Vasculitis and inflammation can affect many organs, explaining the intestinal, hepatological, and renal manifestations. DADA2 should be primarily considered in patients with early-onset fevers, rashes, and strokes even in the absence of positive family history. Hematological manifestations include most commonly hypogammaglobulinemia, although pure red cell aplasia (PRCA), immune thrombocytopenia, and neutropenia have been increasingly reported. Thus, DADA2 may unify a variety of syndromes previously not thought to be related. The first-line treatment consists of TNF-inhibitors and is effective in controlling inflammation and in preserving vascular integrity. Hematopoietic stem cell transplantation (HSCT) has been successful in a group of patients presenting with hematological manifestations. ADA2 is highly expressed in myeloid cells and plays a role in the differentiation of macrophages; however, its function is still largely undetermined. Deficiency of ADA2 has been linked to an imbalance in differentiation of monocytes towards proinflammatory M1 macrophages. Future research on the function of ADA2 and on the pathophysiology of DADA2 will improve our understanding of the condition and promote early diagnosis and targeted treatment.

show abstract

Section: Clinical Presentationmentioning

confidence: 99%

Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment

2018

View full text Add to dashboard Cite

show abstract

“…Ischemic strokes have been reported in more than 50 patients (~38%) and many have experienced recurrent episodes. In some cases, stroke is the initial feature that leads to the diagnosis ( 12 , 39 ). The severity of strokes varies from small lacunar infarcts with minimal sequelae to larger infarcts leading to permanent neurologic impairments and even death ( 40 ).…”

Section: Dada2 As a Monogenic Cause Of Vasculopathymentioning

confidence: 99%

Vasculopathy, Immunodeficiency, and Bone Marrow Failure: The Intriguing Syndrome Caused by Deficiency of Adenosine Deaminase 2

Lee

2018

Front. Pediatr.

View full text Add to dashboard Cite

Deficiency of adenosine deaminase 2 (DADA2) is a monogenic form of systemic vasculopathy that often presents during early childhood. Linked to biallelic mutations in ADA2 (previously CECR1), DADA2 was initially described as a syndrome of recurrent fever, livedo racemosa, early-onset strokes, and peripheral vasculopathy that resembles polyarteritis nodosum. However, the wide spectrum of clinical findings and heterogeneity of disease, even among family members with identical mutations, is increasingly recognized. Evidence of systemic inflammation and vasculopathy is not uniformly present in DADA2 patients and some can remain asymptomatic through adulthood. Humoral immunodeficiency characterized by low immunoglobulin levels and increased risk of infection is another common feature of DADA2. Variable cytopenias including pure red cell aplasia that mimics Diamond-Blackfan anemia can also be primary manifestations of DADA2. How defects in a single gene translate into these heterogeneous presentations remains to be answered. In this review, we will summarize lessons learned from the pleiotropic clinical manifestations of DADA2.

show abstract

“…2 CNS involvement caused by small-and medium-sized vessel vasculopathy is a well-recognized complication, being present in nearly 50% of cases, 6 mostly without anomalies detectable on angiographic studies. 2,[6][7][8][9] Neurologic events usually occur early in the course of the disease, at a very young age, 1,2,6,10 frequently associated with inflammatory flares. 2,10 Affected patients may present with ischemic strokes, distributed in the territory of perforator arteries, or intracranial hemorrhages, often recurrent, leading to clinical manifestations varying from minimal neurologic deficits to fatal outcome.…”

mentioning

confidence: 99%

Widening the Neuroimaging Features of Adenosine Deaminase 2 Deficiency

Geraldo

Caorsi

Tortora

et al. 2021

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

Adenosine deaminase 2 deficiency (OMIM #615688) is an autosomal recessive disorder characterized by a wide clinical spectrum, including small-and medium-sized vessel vasculopathies, but data focusing on the associated neuroimaging features are still scarce in the literature. Here, we describe the clinical neuroimaging features of 12 patients with genetically proven adenosine deaminase 2 deficiency (6 males; median age at disease onset, 1.3 years; median age at genetic diagnosis, 15.5 years). Our findings expand the neuroimaging phenotype of this condition demonstrating, in addition to multiple, recurrent brain lacunar ischemic and/or hemorrhagic strokes, spinal infarcts, and intracranial aneurysms, also cerebral microbleeds and a peculiar, likely inflammatory, perivascular tissue in the basal and peripontine cisterns. Together with early clinical onset, positive family history, inflammatory flares and systemic abnormalities, these findings should raise the suspicion of adenosine deaminase 2 deficiency, thus prompting genetic evaluation and institution of tumor necrosis factor inhibitors, with a potential great impact on neurologic outcome.

show abstract

Stroke as Initial Manifestation of Adenosine Deaminase 2 Deficiency

Cited by 23 publications

References 10 publications

Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment

Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment

Vasculopathy, Immunodeficiency, and Bone Marrow Failure: The Intriguing Syndrome Caused by Deficiency of Adenosine Deaminase 2

Widening the Neuroimaging Features of Adenosine Deaminase 2 Deficiency

Contact Info

Product

Resources

About