A case series of adenosine deaminase 2 deficient patients emphasizing treatment and genotype-phenotype correlations

Batu, Ezgi Deniz; Karadağ, Ömer; Taskiran, EZ; Kalyoncu, Umut; Aksentijevich, Ivona; Alikaşifoğlu, Mehmet; Özen, Seza

doi:10.1186/1546-0096-13-s1-p62

Cited by 14 publications

(20 citation statements)

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“…Of the latter, 3 also had low levels of IgA. Fifteen patients had normal immunoglobulin levels (1,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Three children were described as having increased immunoglobulin levels (7,19), including 2 patients with a deletion encompassing CECR1 and IL17RA, who cannot be compared directly to the other patients with mutations in CECR1 only.…”

Section: Discussionmentioning

confidence: 99%

Screening of 181 Patients With Antibody Deficiency for Deficiency of Adenosine Deaminase 2 Sheds New Light on the Disease in Adulthood

Schepp

Proietti

Frede

et al. 2017

Arthritis & Rheumatology

111

109

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Taken together, our findings indicate that DADA2 presents not only with vasculopathy but also with an immunodeficiency of the B cell compartment. Therefore, patients with antibody deficiency should be screened for DADA2. Anti-tumor necrosis factor treatment might improve immunologic features over time and might be considered in patients without vascular manifestations but with elevated inflammation markers. Conservative management has so far proven to be the choice for our less severely affected adolescent and adult DADA2 patients; however, in patients with severe cytopenias and bone marrow failure, hematopoietic stem cell transplantation should be considered.

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Section: Discussionmentioning

confidence: 99%

Screening of 181 Patients With Antibody Deficiency for Deficiency of Adenosine Deaminase 2 Sheds New Light on the Disease in Adulthood

Schepp

Proietti

Frede

et al. 2017

Arthritis & Rheumatology

111

109

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“…1 In the severe spectrum of the disease are patients presenting with cranial nerve palsy, diplegia, paraplegia, peripheral polyneuropathy due to perineuritis, ataxia, sensorineural hearing loss, mononeuritis multiplex, labyrinthitis, neuromyelitis, encephalopathy and cerebral atrophy. 1,2,73,74,76,79,81,82 At the histology level, the brain lesions correspond to erythrocyte extravasation in brain parenchyma.…”

Section: Vasculitismentioning

confidence: 99%

“…One patient with DADA2-PAN was treated with colchicine, as he was also a carrier for a familial Mediterranean fever-associated mutation. 76 Anti-interleukin-1 therapy with anakinra or canakinumab was not successful. Anti-IL6 treatment (tocilizumab) used in a patient with Castleman syndrome, who had high IL-6 serum levels, was successful but resulted in relapses with stroke in others.…”

Section: Iag Nos Ismentioning

confidence: 99%

“…Pathology has shown a common variable immunodeficiency (CVID) inflammatory bowel disease like findings with paucity of plasma cells 68. Additionally, intestinal necrosis, perforations, and intestinal vessel aneurysm have been reported 1,2,68,74,76,78,96. Hepatic involvement is probably an underestimated feature of DADA2.…”

mentioning

confidence: 99%

“…Hepatic involvement is probably an underestimated feature of DADA2. Elevated transaminases, hepatosplenomegaly, and portal hypertension have been noted in many patients.Histological analysis of the liver biopsy typically shows the nodular regenerative hyperplasia and/or hepatoportal sclerosis 1,76,96.…”

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confidence: 99%

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Human adenosine deaminase 2 deficiency: A multi‐faceted inborn error of immunity

Moens

Hershfield

Arts

et al. 2018

Immunological Reviews

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Human adenosine deaminase 1 deficiency was described in the 1970s to cause severe combined immunodeficiency. The residual adenosine deaminase activity in these patients was attributed to adenosine deaminase 2. Human adenosine deaminase type 2 deficiency (DADA2), due to biallelic deleterious mutations in the ADA2 gene, is the first described monogenic type of small‐ and medium‐size vessel vasculitis. The phenotype of DADA2 also includes lymphoproliferation, cytopenia, and variable degrees of immunodeficiency. The physiological role of ADA2 is still enigmatic hence the pathophysiology of the condition is unclear. Preliminary data showed that in the absence of ADA2, macrophage differentiation is skewed to a pro‐inflammatory M1 subset, which is detrimental for endothelial integrity. The inflammatory phenotype responds well to anti‐TNF therapy with etanercept and that is the first‐line treatment for prevention of severe vascular events including strokes. The classic immunosuppressive drugs are not successful in controlling the disease activity. However, hematopoietic stem cell transplantation (HSCT) has been shown to be a definitive cure in DADA2 patients who present with a severe cytopenia. HSCT can also cure the vascular phenotype and is the treatment modality for patients’ refractory to anti‐cytokine therapies. In this review, we describe what is currently known about the molecular mechanisms of DADA2. Further research on the pathophysiology of this multifaceted condition is needed to fine‐tune and steer future therapeutic strategies.

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ADA2 deficiency in a patient with Noonan syndrome‐like disorder with loose anagen hair: The co‐occurrence of two rare syndromes

Doğan

Şimşek‐Kiper

Taşkıran

et al. 2019

American J of Med Genetics Pt A

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Noonan syndrome-like disorder with loose anagen hair (NS/LAH) is one of the RASopathies, a group of clinically related developmental disorders caused by germline mutations in genes that encode components acting in the RAS/MAPK pathway. Among RASopathies, NS/LAH (OMIM 607721) is an extremely rare, multiple anomaly syndrome characterized by dysmorphic facial features similar to those observed in Noonan syndrome along with some distinctive ectodermal findings including easily pluckable, sparse, thin, and slow-growing hair. ADA2 deficiency (DADA2, OMIM 615688) is a monogenic autoinflammatory disorder caused by homozygous or compound heterozygous mutations in ADA2, with clinical features including recurrent fever, livedo racemosa, hepatosplenomegaly, and strokes as well as immune dysregulation. This is the first report of NS/LAH and ADA2 deficiency in the same individual. We report on a patient presenting with facial features, recurrent infections and ectodermal findings in whom both the clinical and molecular diagnoses of NS/LAH and ADA2 deficiency were established, respectively. K E Y W O R D SADA2, consanguinity, DADA2, Noonan syndrome-like disorder with loose anagen hair, SHOC2

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A case series of adenosine deaminase 2 deficient patients emphasizing treatment and genotype-phenotype correlations

Cited by 14 publications

References 0 publications

Screening of 181 Patients With Antibody Deficiency for Deficiency of Adenosine Deaminase 2 Sheds New Light on the Disease in Adulthood

Screening of 181 Patients With Antibody Deficiency for Deficiency of Adenosine Deaminase 2 Sheds New Light on the Disease in Adulthood

Human adenosine deaminase 2 deficiency: A multi‐faceted inborn error of immunity

ADA2 deficiency in a patient with Noonan syndrome‐like disorder with loose anagen hair: The co‐occurrence of two rare syndromes

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