PB0269 - Single center case series & literature review: Deficiency of Adenosine Desaminase (DADA2) causes stroke, livedo racemosa, fever, lymphoproliferation, immunoglobulin deficiency&pancytopenia in children

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Madlen Reschke, MD

Physician
University Medicine, Charite, Berlin, Germany
Berlin, Berlin, Germany

Co-Author(s)

HB

Horst Von Bernuth

Physician
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Berlin, Berlin, Germany.Labor Berlin GmbH, Immunology, Berlin, Berlin, Germany.
Berlin, Berlin, Germany
SH

Susanne Holzhauer

MD
Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie, Universitätsmedizin Berlin.
Berlin, Berlin, Germany
TK

Tilman Kallinich

Physician
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Berlin, Berlin, Germany. Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Rheumatology, Berlin, Berlin, Germany.
Berlin, Berlin, Germany

Background: Cryptogenic pediatric stroke is rare. DADA2 has recently been identified as a possible cause. The monogenetic (ADA21), multisystemic, autoinflammatory disease manifests mainly as cytopenia, antibody deficiency or localized vasculitis causing ischemic strokes, often in the lacunar brain stem area5.
TNF α is highly efficacious2, 5 in suppressing symptoms; only stem cell transplantation is curative3. Most common differential diagnosis are “CVID, ALPS - like, pancytopenia, or low IgG”.

Aims: Raising awareness for rare causes of pediatric stroke.

Methods: Collecting and analyzing data on all children who have been diagnosed with DADA2 at our center, focusing on incidence of cerebral ischemia, first symptoms and treatment success.

Results: In six children DADA2 was genetically confirmed at our center (4x compound heterozygous, 2x homozygous variation in ADA2). Median time to diagnosis: 3.5 years. Symptoms at presentation were typical4: livedo, immunoglobin-deficiency, cytopenia, fever of unknown origin, panniculitis/myositis, lymphoproliferation and failure to thrive (n=6,4,4,3,3,1,1 respectively).
Lacunar stroke as first symptom occurred twice in two patients, causing hemiparesis, diplopia, coma, vertigo, cranial nerve paralysis and aphasia. All were treated with a TNF α inhibitor. Median time of follow up is: 13,5 months. Lost to follow-up: 2/6 (siblings).
After starting treatment, no further ischemic cerebral events or other symptoms were observed. Persisting laboratory abnormalities: mild leukopenia and immunoglobulin deficiency (n=2,3 respectively).

Conclusion(s): DADA2 is a treatable, potentially life threatening disease that can cause recurrent stroke and other dangerous complications; even in young children. Pediatric patients with stroke should be screened for ostensibly unrelated symptoms in order to determine if genetic analysis is indicated.