Published 2017
| Version v1
Publication
ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study
Creators
- Caorsi, Roberta
- Penco, Federica
- Grossi, Alice
- Insalaco, Antonella
- Omenetti, Alessia
- Alessio, Maria
- Conti, Giovanni
- Marchetti, Federico
- Picco, Paolo
- Tommasini, Alberto
- Martino, Silvana
- Malattia, Clara
- Gallizi, Romina
- Podda, Rosa Anna
- Salis, Annalisa
- Falcini, Fernanda
- Schena, Francesca
- GARBARINO, FRANCESCA
- Morreale, Alessia
- Pardeo, Manuela
- Ventrici, Claudia
- Passarelli, Chiara
- Zhou, Qing
- Severino, Mariasavina
- Gandolfo, Carlo
- Damonte, Gianluca
- Martini, Alberto
- Ravelli, Angelo
- Aksentijevich, Ivona
- Ceccherini, Isabella
- Gattorno, Marco
Contributors
Others:
- Caorsi, Roberta
- Penco, Federica
- Grossi, Alice
- Insalaco, Antonella
- Omenetti, Alessia
- Alessio, Maria
- Conti, Giovanni
- Marchetti, Federico
- Picco, Paolo
- Tommasini, Alberto
- Martino, Silvana
- Malattia, Clara
- Gallizi, Romina
- Podda, Rosa Anna
- Salis, Annalisa
- Falcini, Fernanda
- Schena, Francesca
- Garbarino, Francesca
- Morreale, Alessia
- Pardeo, Manuela
- Ventrici, Claudia
- Passarelli, Chiara
- Zhou, Qing
- Severino, Mariasavina
- Gandolfo, Carlo
- Damonte, Gianluca
- Martini, Alberto
- Ravelli, Angelo
- Aksentijevich, Ivona
- Ceccherini, Isabella
- Gattorno, Marco
Description
Objectives 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.
Methods 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.
Results 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 24months (6months 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.
Conclusions 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.
Additional details
Identifiers
- URL
- http://hdl.handle.net/11567/896078
- URN
- urn:oai:iris.unige.it:11567/896078
Origin repository
- Origin repository
- UNIGE