biochimica clinica

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OPINIONI - Opinions

Volume:

Biochimica Clinica, 2024; 48(1) 62-66

Pubblicato on-line:

February 2, 2024

DOI:

10.19186/BC_2024.004

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Autenticazione richiesta

Proposta di un algoritmo diagnostico per il deficit di Adenosina Deaminasi-2 (DADA2)

AUTORI

Alessia Cafaro1, Alice Grossi2, Sebastiano Barco1, Federica Pigliasco1, Margherita Biondi1, Francesca Schena3, Federica Penco3, Sara Signa3, Enrico Drago4, Caterina Matucci-Cerinic4, Stefano Volpi3, Roberta Caorsi3, Roberto Bandettini1, Isabella Ceccherini2, Marco Gattorno3, Giuliana Cangemi1
1IRCCS Istituto Giannina Gaslini, U.O.C. Laboratorio Centrale di Analisi Settore Cromatografia e Spettrometria di Massa, Genova
2Genetica e Genomica delle Malattie Rare , IRCCS Istituto Giannina Gaslini, Genova
3UOC Reumatologia e Malattie Autoinfiammatorie, IRCCS Istituto Giannina Gaslini, Genova
4Dip. di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno infantili (DINOGMI), Università di Genova

ABSTRACT

Diagnostic workflow for Adenosine Deaminase-2 Deficiency (DADA2): a proposal

Deficiency of Adenosine deaminase 2 (DADA2) is a monogenic autoinflammatory disease caused by homozygous or compound heterozygous mutations in the ADA2 gene (formerly CECR1 Cat Eye Syndrome Chromosome Region 1). Clinical manifestations of DADA2 are highly variable and include systemic inflammation with fever, early stroke, vasculopathy, immune dysregulation (hypogammaglobulinemia, lymphoproliferation, increased rate of infections), and hematologic abnormalities (pure red cell aplasia, bone marrow failure, cytopenias). The most promising treatments are anti-TNF inhibitors, the only drugs that can prevent the serious consequences of the disease. Early diagnosis is therefore critical. DADA2 can be diagnosed by genetic analysis or functional tests (biochemical diagnosis) that allow the enzyme activity to be assayed. At the Giannina Gaslini Institute, a children’s hospital in Italy, a method based on liquid chromatography coupled with tandem mass spectrometry has been developed to measure enzyme activity. A diagnostic workflow is adopted at the institute that involves the assay of ADA2 activity followed by genetic confirmation when the biochemical test is altered.

 

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