ADA2 Deficiency: Case Series of Five Patients with Varying Phenotypes

Tanatar, Ayşe; Karadağ, Şerife Gül; Sözeri, Betül; Sönmez, Hafize Emine; Çakan, Mustafa; Demirkol, Yasemin Kendir; Ayaz, Nuray Aktay

doi:10.1007/s10875-019-00734-0

Cited by 17 publications

(19 citation statements)

References 15 publications

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“…Two patients (Patients 31 & 37) developed an idiopathic cardiomyopathy, a clinical feature described in at least one other patient in the literature ( 17 ). Coronary artery calcifications were observed in a 26-year-old (Patient 49) with no other known risk factors and may represent post-vasculitis sequelae.…”

Section: Resultsmentioning

confidence: 93%

“…The mean follow-up of this cohort at the NIH was 5.04 years (1.58-17.35 years) excluding 3 patients who required prolonged hospitalization following HCT. The mean number of NIH clinic visits was 4.21 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). The clinical and laboratory features of the patients are summarized in Table 1.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

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The Spectrum of the Deficiency of Adenosine Deaminase 2: An Observational Analysis of a 60 Patient Cohort

et al. 2022

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The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease that has undergone extensive phenotypic expansion since being first described in patients with fevers, recurrent strokes, livedo racemosa, and polyarteritis nodosa in 2014. It is now recognized that patients may develop multisystem disease that spans multiple medical subspecialties. Here, we describe the findings from a large single center longitudinal cohort of 60 patients, the broad phenotypic presentation, as well as highlight the cohort’s experience with hematopoietic cell transplantation and COVID-19. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory, and hematologic, however, most patients presented with significant overlap between these three phenotype groups. The cardinal features of the inflammatory/vascular group included cutaneous manifestations and stroke. Evidence of immune dysregulation was commonly observed, including hypogammaglobulinemia, absent to low class-switched memory B cells, and inadequate response to vaccination. Despite these findings, infectious complications were exceedingly rare in this cohort. Hematologic findings including pure red cell aplasia (PRCA), immune-mediated neutropenia, and pancytopenia were observed in half of patients. We significantly extended our experience using anti-TNF agents, with no strokes observed in 2026 patient months on TNF inhibitors. Meanwhile, hematologic and immune features had a more varied response to anti-TNF therapy. Six patients received a total of 10 allogeneic hematopoietic cell transplant (HCT) procedures, with secondary graft failure necessitating repeat HCTs in three patients, as well as unplanned donor cell infusions to avoid graft rejection. All transplanted patients had been on anti-TNF agents prior to HCT and received varying degrees of reduced-intensity or non-myeloablative conditioning. All transplanted patients are still alive and have discontinued anti-TNF therapy. The long-term follow up afforded by this large single-center study underscores the clinical heterogeneity of DADA2 and the potential for phenotypes to evolve in any individual patient.

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Section: Resultsmentioning

confidence: 93%

Section: Clinical Manifestationsmentioning

confidence: 99%

The Spectrum of the Deficiency of Adenosine Deaminase 2: An Observational Analysis of a 60 Patient Cohort

et al. 2022

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“…Azathioprine, cyclosporine, tacrolimus, cyclophosphamide and methotrexate have all been used with little success. Anti‐tumor necrosis factor and hematopoietic stem‐cell therapy are beneficial for controlling fever episodes and vasculopathy and for stroke prevention [23,24]. Unlike the standard of care for stroke patients, the use of aspirin and anticoagulants is discouraged as hemorrhagic strokes are a potential complication [19].…”

Section: Methodsmentioning

confidence: 99%

Livedo racemosa in neurological diseases: an update on the differential diagnoses

Mitri

Enk

Bersano

et al. 2020

Euro J of Neurology

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Livedo is a net‐like violaceous skin pattern. It can be classified as physiological or pathological. The physiological livedo reticularis usually appears in cold conditions, whereas the pathological and irregular livedo, which persists in warm temperatures, is often labeled as ‘livedo racemosa’. Some neurological pathologies are associated with livedo, most commonly those with an inflammatory component or those derived from systemic disorders. The present review summarizes the most important central and peripheral neurological diseases in pediatric and adult age groups associated with livedo, providing physicians with an overview of the clinical presentation, etiology, diagnosis and management of these conditions.

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“…These ophthalmologic features were likely to be contributed by possible central retinal artery involvement and third cranial nerve palsies after small initially undetectable strokes. Ocular inflammation (uveitis, scleritis, and episcleritis) ( 23 ), ptosis, and nystagmus were also documented ( 19 , 24 ). So far, there have not been reports about a DADA2 patient displaying retinal vasculitis resembling FBA.…”

Section: Discussionmentioning

confidence: 99%

Case Report: An Adult Patient With Deficiency of Adenosine Deaminase 2 Resembled Unilateral Frosted Branch Angiitis

Shan

et al. 2021

Front. Med.

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Purpose: Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive systemic autoinflammatory disorder. We describe a rare case of an adult patient with DADA2 who presented with unilateral frosted branch angiitis (FBA) combined with branch retinal vein occlusion and panuveitis.Method: This paper is a clinical case report.Results: A 31-year-old male patient complained of blurred vision in his right eye for 2 days. His fundus examination showed FBA combined with branch retinal vein occlusion and panuveitis. He had a medical history of intermittent and recurrent fever, skin rash and aphthous ulcer for 5 years, and lacunar infarction for 1 month. Laboratory examinations showed hypogammaglobulinemia and mild prolonged activated partial thromboplastin time (APTT). Brain magnetic resonance imaging (MRI) revealed old lacunar infarction in the right basal ganglia and the lateral ventricle and fresh lacunar infarction in the right pons, respectively. The perivascular sheathing of FBA and macular edema were resolved after steroid administration and treatment of intravitreal anti-VEGF injection. During the period of follow-up, the patient subsequently suffered from recurrence of strokes, abnormality of coagulation function, sudden hearing loss of the left ear, and diplopia. His gene sequencing results demonstrated several deletion mutations in ADA2, and the diagnosis of DADA2 was eventually confirmed.Conclusions: FBA represents a very rare ocular feature of DADA2 and may in some cases be the presenting manifestation. Therefore, ophthalmologists need to be aware of this rare autoinflammatory disease.

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ADA2 Deficiency: Case Series of Five Patients with Varying Phenotypes

Cited by 17 publications

References 15 publications

The Spectrum of the Deficiency of Adenosine Deaminase 2: An Observational Analysis of a 60 Patient Cohort

The Spectrum of the Deficiency of Adenosine Deaminase 2: An Observational Analysis of a 60 Patient Cohort

Livedo racemosa in neurological diseases: an update on the differential diagnoses

Case Report: An Adult Patient With Deficiency of Adenosine Deaminase 2 Resembled Unilateral Frosted Branch Angiitis

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