Abstract
Adenosine Deaminase 2 Deficiency (DADA2) (OMIM: 607575) is a monogenic, autoinflammatory disease caused by the loss of functional homozygous or heterozygous mutations in the ADA 2 gene (previously CECR1, Cat Eye Syndrome Chromosome Region 1). A timely diagnosis is crucial to start Anti-TNF therapies that are efficacious in controlling the disease. The confirmation of DADA2 is based on DNA sequencing and enzymatic assay. It is, thus, very important to have robust and reliable assays that can be rapidly utilized in specialized laboratories that can centralize samples from other centers. In this paper, we show a novel enzymatic assay based on liquid chromatography-tandem mass spectrometry that allows the accurate determination of the ADA2 enzyme activity starting from very small amounts of plasma spotted on filter paper (dried plasma spot). The method allows significantly distinguishing healthy controls from affected patients and carriers and could be of help in implementing the diagnostic workflow of DADA2.
Highlights
The Deficiency of Adenosine Deaminase 2 (DADA2) (OMIM: 607575) is a monogenic, autoinflammatory disease caused by the loss of functional homozygous or heterozygous mutations in the ADA 2 gene [1,2]
We describe for the first time a method based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), which allows the fast and reliable determination of ADA2 activity on dried plasma spot (DPS), starting from a very little amount (50 μL) of sample
It is important to note that the genetic analysis of ADA2 gene could be rather laborious
Summary
The Deficiency of Adenosine Deaminase 2 (DADA2) (OMIM: 607575) is a monogenic, autoinflammatory disease caused by the loss of functional homozygous or heterozygous mutations in the ADA 2 gene (previously CECR1 Cat Eye Syndrome Chromosome Region 1) [1,2]. DADA2 is characterized by a wide phenotypic and clinical variability. Presentation of the disease includes an early-onset vasculopathy with clinical and histopathological features of polyarteritis nodosa (PAN), associated with hemorrhagic and ischemic strokes. Immunologic and hematologic abnormalities including hypogammaglobulinemia with reduction of memory and terminally differentiated B cells and plasma cells have been described in about half the patients with DADA2 [3]. A severe clinical picture dominated by cytopenia and lymphoproliferation has been described. Even if the disease’s onset is commonly in the pediatric age, some patients with adulthood onset have been described as well [4]. The clinical course can be chronic or characterized by recurrent flares of systemic inflammation during which the most severe clinical manifestations were described [1]
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