Diagnosis and management of ADA2 deficient polyarteritis nodosa.

Deficiency of ADA2 (DADA2) is a recently described systemic inflammatory vasculopathy caused by mutations in the CERC1 gene that often, but not always, clinically resembles polyarteritis nodosa (PAN). The condition was originally characterized by livedoid rash, systemic inflammation, variable hypogammaglobulinemia, and early-onset stroke. The phenotypic spectrum has expanded to include patients with immunodeficiency syndromes and bone marrow dysfunction, which are not typical features of PAN. Exploration into the pathogenesis and treatment options of DADA2 has added to our understanding of this condition, but more studies are needed. The purpose of this article is to review the various clinical phenotypes of DADA2, and raise awareness among rheumatologists to consider DADA2 when evaluating patients presenting with PAN-like disease.

Human A ，Pagnoux C 《-》

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

Meyts I ，Aksentijevich I 《-》

A Monogenic Disease with a Variety of Phenotypes: Deficiency of Adenosine Deaminase 2.

Özen S ，Batu ED ，Taşkıran EZ ，Özkara HA ，Ünal Ş ，Güleray N ，Erden A ，Karadağ Ö ，Gümrük F ，Çetin M ，Sönmez HE ，Bilginer Y ，Ayvaz DÇ ，Tezcan I ... -  《-》

Deficiency of Adenosine Deaminase 2 (DADA2), an Inherited Cause of Polyarteritis Nodosa and a Mimic of Other Systemic Rheumatologic Disorders.

Hashem H ，Kelly SJ ，Ganson NJ ，Hershfield MS ... -  《-》

ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study.

To analyse the prevalence of CECR1 mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes in the context of inflammation or polyarteritis nodosa (PAN). Forty-eight patients from 43 families were included in the study. Direct sequencing of CECR1 was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity was analysed in monocyte isolated from patients and healthy controls incubated with adenosine and with or without an ADA1 inhibitor. Biallelic homozygous or compound heterozygous CECR1 mutations were detected in 15/48 patients. A heterozygous disease-associated mutation (p.G47V) was observed in two affected brothers. The mean age of onset of the genetically positive patients was 24 months (6 months to 7 years). Ten patients displayed one or more cerebral strokes during their disease course. Low immunoglobulin levels were detected in six patients. Thalidomide and anti-TNF (tumour necrosis factor) blockers were the most effective drugs. Patients without CECR1 mutations had a later age at disease onset, a lower prevalence of neurological and skin manifestations; one of these patients displayed all the clinical features of adenosine deaminase 2deficiency (DADA2) and a defective enzymatic activity suggesting the presence of a missed mutation or a synthesis defect. DADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist. Timely diagnosis and treatment with anti-TNF agents are crucial for the prevention of severe complications of the disease. Functional assay to measure ADA2 activity should complement genetic testing in patients with non-confirming genotypes.

Caorsi R ，Penco F ，Grossi A ，Insalaco A ，Omenetti A ，Alessio M ，Conti G ，Marchetti F ，Picco P ，Tommasini A ，Martino S ，Malattia C ，Gallizzi R ，Podda RA ，Salis A ，Falcini F ，Schena F ，Garbarino F ，Morreale A ，Pardeo M ，Ventrici C ，Passarelli C ，Zhou Q ，Severino M ，Gandolfo C ，Damonte G ，Martini A ，Ravelli A ，Aksentijevich I ，Ceccherini I ，Gattorno M ... -  《-》