Two cases of ADA2 deficiency presenting as childhood polyarteritis nodosa: novel ADA2 variant, atypical CNS manifestations, and literature review

Ganhão, Sara; Loureiro, Graça; Oliveira, Diana Rita; Dos-Reis-Maia, Rúben; Aguiar, Francisca; Quental, Rita; Moura, Carla Pinto; Barreira, João C.M.; Rodrigues, Mariana; Brito, Iva

doi:10.1007/s10067-020-05210-4

Cited by 17 publications

(26 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This suggests a possible underestimation of these subtle findings if brain MR imaging studies are not performed in the acute stage or with high spatial resolution sequences. As previously identified in a few patients with DADA2, 14,15 we found an additional small ischemic medullary infarct at the cervical level in 1 patient. Of note, spinal cord involvement in individuals with DADA2 might also be underrated because only a minority of patients underwent a spinal MR imaging in both the current and in Bulut et al's series.…”

Section: Discussionsupporting

confidence: 85%

“…Before treatment with anti-TNF, thalidomide, or both, new ischemic lesions developed in half of patients at follow-up studies. 4,7,13,15 Conversely, no new neurologic events or MR imaging lesions were noticed afterward, except for 2 recurrences shortly after introduction of anti-TNF or temporary discontinuation of thalidomide. Of note, the prevalence of ischemic strokes in our cohort was similar to that reported by Bulut et al 14 in patients with DADA2-related vasculopathy and was expectedly higher than that described in a review also including patients with purely hematologic phenotypes (around 40%).…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

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

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 96%

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

show abstract

“…Mild manifestations (e.g. lymphopenia) may respond to TNF-blockers ( 66 – 68 ); however, TNF-blockade is ineffective for treatment of severe hematological manifestations (e.g. bone marrow failure and PRCA/DBA) ( 33 , 35 ).…”

Section: Overview Of Treatment In Dada2mentioning

confidence: 99%

Deficiency of Human Adenosine Deaminase Type 2 – A Diagnostic Conundrum for the Hematologist

et al. 2022

View full text Add to dashboard Cite

Deficiency of adenosine deaminase type 2 (DADA2) was first described in 2014 as a monogenic cause of polyartertitis nodosa (PAN), early onset lacunar stroke and livedo reticularis. The clinical phenotype of DADA2 is, however, very broad and may involve several organ systems. Apart from vasculitis, children may present with i) Hematological manifestations (ii) Lymphoproliferation and iii) Immunodeficiencies. Patients with DADA2 can have variable patterns of cytopenias and bone marrow failure syndromes. Patients with DADA2 who have predominant haematological manifestations are associated with ADA2 gene variants that result in minimal or no residual ADA2 activity. Lymphoproliferation in patients with DADA2 may range from benign lymphoid hyperplasia to lymphoreticular malignancies. Patients may present with generalized lymphadenopathy, splenomegaly, autoimmune lymphoproliferative syndrome (ALPS) like phenotype, Hodgkin lymphoma, T-cell large granular lymphocytic infiltration of bone marrow and multicentric Castleman disease. Immunodeficiencies associated with DADA are usually mild. Affected patients have variable hypogammaglobulinemia, decrease in B cells, low natural killer cells, common variable immunodeficiency and rarely T cell immunodeficiency. To conclude, DADA2 has an extremely variable phenotype and needs to be considered as a differential diagnosis in diverse clinical conditions. In this review, we describe the evolving clinical phenotypes of DADA2 with a special focus on haematological and immunological manifestations.

show abstract

“…Instead, DADA2 is mainly associated with lacunar and hemorrhagic strokes caused by endothelial dysfunction and vascular frailty. Strikingly, one case report described spinal cord ischemia in a DADA2 patient ( 52 ). Non-vasculitic stroke has also been associated with FMF and VEXAS syndrome ( 40 , 47 , 49 ).…”

Section: Central Nervous System Manifestations Of Autoinflammatory Di...mentioning

confidence: 99%

Central nervous system manifestations of monogenic autoinflammatory disorders and the neurotropic features of SARS-CoV-2: Drawing the parallels

2022

View full text Add to dashboard Cite

Central nervous system (CNS) involvement in monogenic autoinflammatory disorders (AID) is increasingly recognized and can be life threatening. Therefore, a low threshold to consider CNS disease should be maintained in patients with systemic inflammation. Hyperinflammation is also a key feature of severe acute COVID-19 and post COVID-19 entities such as multisystem inflammatory syndrome in children. Like AID, COVID-19 patients can present with severe CNS involvement. The impact of COVID-19 on AID and CNS involvement in particular is still obscure, nevertheless dreaded. In the current review, we synthesize the spectrum of CNS manifestations in monogenic AID. We explore common pathophysiological and clinical features of AID and COVID-19. Moreover, we assess the impact of immune dysregulation associated with SARS-CoV-2 infections and post COVID-19 hyperinflammation in AID. The striking commonalities found between both disease entities warrant caution in the management of AID patients during the current pandemic.

show abstract

Two cases of ADA2 deficiency presenting as childhood polyarteritis nodosa: novel ADA2 variant, atypical CNS manifestations, and literature review

Cited by 17 publications

References 18 publications

Widening the Neuroimaging Features of Adenosine Deaminase 2 Deficiency

Widening the Neuroimaging Features of Adenosine Deaminase 2 Deficiency

Deficiency of Human Adenosine Deaminase Type 2 – A Diagnostic Conundrum for the Hematologist

Central nervous system manifestations of monogenic autoinflammatory disorders and the neurotropic features of SARS-CoV-2: Drawing the parallels

Contact Info

Product

Resources

About