Neurological phenotype of adenosine deaminase 2 deficient patients: a cohort study

Merelijne A. Verschoof; Laura C. C. van Meenen; M. Valérie E. Andriessen; Daniëlle M. C. Brinkman; Sylvia Kamphuis; Taco W. Kuijpers; Helen L. Leavis; G. Elizabeth Legger; Catharina M. Mulders‐Manders; Anne P. J. de Pagter; Abraham Rutgers; Gijs T. J. van Well; Jonathan M. Coutinho; A. Elisabeth Hak; Joris M. van Montfrans; Femke C. C. Klouwer

doi:10.1111/ene.16043

journal article Open Access Aug 29, 2023

Neurological phenotype of adenosine deaminase 2 deficient patients: a cohort study

Merelijne A. Verschoof

Laura C. C. van Meenen

M. Valérie E. Andriessen Daniëlle M. C. Brinkman Sylvia Kamphuis Taco W. Kuijpers

Helen L. Leavis G. Elizabeth Legger Catharina M. Mulders‐Manders Anne P. J. de Pagter Abraham Rutgers

Gijs T. J. van Well Jonathan M. Coutinho

A. Elisabeth Hak Joris M. van Montfrans Femke C. C. Klouwer

European Journal of Neurology Vol. 31 No. 1 · Wiley

View at Publisher Save 10.1111/ene.16043

Abstract

AbstractBackground and purposePatients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischaemic and hemorrhagic stroke, but less clearly defined neurological symptoms have also been reported.MethodsIn this cohort study, patients with confirmed ADA2 deficiency from seven university hospitals in the Netherlands were included. The frequency and recurrence rates of neurological manifestations before and after initiation of tumor necrosis factor α (TNF‐α) inhibiting therapy were analyzed.ResultsTwenty‐nine patients were included with a median age at presentation of 5 years (interquartile range 1–17). Neurological manifestations occurred in 19/29 (66%) patients and were the presenting symptom in 9/29 (31%) patients. Transient ischaemic attack (TIA)/ischaemic stroke occurred in 12/29 (41%) patients and was the presenting symptom in 8/29 (28%) patients. In total, 25 TIAs/ischaemic strokes occurred in 12 patients, one after initiation of TNF‐α inhibiting therapy and one whilst switching between TNF‐α inhibitors. None was large‐vessel occlusion stroke. Two hemorrhagic strokes occurred: one aneurysmatic subarachnoid hemorrhage and one spontaneous intracerebral hemorrhage. Most neurological symptoms, including cranial nerve deficits, vertigo, ataxia and seizures, were caused by TIAs/ischaemic strokes and seldom recurred after initiation of TNF‐α inhibiting therapy.ConclusionsNeurological manifestations, especially TIA/ischaemic stroke, are common in patients with ADA2 deficiency and frequently are the presenting symptom. Because it is a treatable cause of young stroke, for which antiplatelet and anticoagulant therapy are considered contraindicated, awareness amongst neurologists and pediatricians is important. Screening for ADA2 deficiency in young patients with small‐vessel ischaemic stroke without an identified cause should be considered.

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Details

Published: Aug 29, 2023
Vol/Issue: 31(1)
License: View

Authors

M

Merelijne A. Verschoof

Department of Neurology HagaZiekenhuis The Hague The Netherlands

L

Laura C. C. van Meenen

Department of Neurology Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands

M

M. Valérie E. Andriessen

Department of Pediatric Immunology and Infectious Diseases University Medical Center Utrecht Utrecht The Netherlands

D

Daniëlle M. C. Brinkman

Department of Pediatrics Willem‐Alexander Children's Hospital, Leiden University Medical Center Leiden The Netherlands

S

Sylvia Kamphuis

Department of Pediatric Rheumatology Sophia Children's Hospital, Erasmus University Medical Center Rotterdam Rotterdam The Netherlands

T

Taco W. Kuijpers

Department of Pediatric Immunology and Infectious Diseases Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands

H

Helen L. Leavis

Department of Rheumatology and Clinical Immunology University Medical Center and Utrecht University Utrecht The Netherlands

G

G. Elizabeth Legger

Department of Pediatric Rheumatology and Immunology University Groningen, University Medical Center Groningen Groningen The Netherlands

C

Catharina M. Mulders‐Manders

Department of Internal Medicine, Radboud Expertise Center for Immunodeficiency and Autoinflammation Radboud University Medical Center Nijmegen The Netherlands

A

Anne P. J. de Pagter

Department of Pediatrics Willem‐Alexander Children's Hospital, Leiden University Medical Center Leiden The Netherlands

A

Abraham Rutgers

Department of Rheumatology and Clinical Immunology University Groningen, University Medical Center Groningen Groningen The Netherlands

G

Gijs T. J. van Well

Division of Pediatric Infectious Diseases, Immunology & Rheumatology, Department of Pediatrics Maastricht University Medical Center Maastricht The Netherlands

J

Jonathan M. Coutinho

Department of Neurology Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands

A

A. Elisabeth Hak

Departments of Internal Medicine and Rheumatology and Clinical Immunology Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands

J

Joris M. van Montfrans

Department of Pediatric Immunology and Infectious Diseases University Medical Center Utrecht Utrecht The Netherlands

F

Femke C. C. Klouwer

Department of Neurology Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands; Department of Pediatric Neurology Emma Children's Hospital, Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands

Cite This Article

Merelijne A. Verschoof, Laura C. C. van Meenen, M. Valérie E. Andriessen, et al. (2023). Neurological phenotype of adenosine deaminase 2 deficient patients: a cohort study. European Journal of Neurology, 31(1). https://doi.org/10.1111/ene.16043

Neurological phenotype of adenosine deaminase 2 deficient patients: a cohort study

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