A novel frameshift variant in the ADA2 gene of a patient with a neurological phenotype: a case report.
Autoinflammatory syndromes
Case report
Deficiency of adenosine deaminase 2
Immunodeficiency
Stroke
Vasculitis
Journal
Pediatric rheumatology online journal
ISSN: 1546-0096
Titre abrégé: Pediatr Rheumatol Online J
Pays: England
ID NLM: 101248897
Informations de publication
Date de publication:
17 Dec 2022
17 Dec 2022
Historique:
received:
27
09
2022
accepted:
25
11
2022
entrez:
17
12
2022
pubmed:
18
12
2022
medline:
21
12
2022
Statut:
epublish
Résumé
Adenosine deaminase 2 (ADA2) deficiency is an inherited autoinflammatory syndrome caused by a defect in the ADA2 gene. Most common manifestations include peripheral vasculopathy, early-onset stroke, immunodeficiency, and haematological manifestations. Patients with pathogenic variants that are more detrimental to ADA2's enzymatic function (e.g. frameshift) have been reported to be prone to developing hematological phenotype. We report here the case of a 13-year-old Caucasian girl with a novel frameshift variant in the ADA2 gene and a clinical phenotype of early-onset stroke. The patient was admitted to hospital with complaints of weakness in her right arm, unilateral facial weakness and speech problems. Her initial laboratory workup was normal; however, magnetic resonance imaging of her brain confirmed acute/subacute ischaemic changes in the posterior limb of the left-sided internal capsule and in the apical part of the thalamus. She also had manifestations of immunodeficiency - recurrent skin infections and otitis, chronic Molluscum contagiosum infection in anamnesis and B cell deficiency with a low level of serum IgA. The patient's DNA was analysed and two pathogenic variants were identified in the ADA2 gene, confirming a diagnosis of adenosine deaminase 2 (ADA2) deficiency. While one of the variants (c.506G > A (p.Arg169Gln)) has been reported previously, the other one is a novel frameshift variant, namely, c.464del (p.Pro155Hisfs*29). The patient received stroke rehabilitation, which significantly improved her functional state. Tumour necrosis factor inhibitor and methotrexate treatment was commenced, and the patient has remained stable with no further ischaemic events. Although rare, ADA2 deficiency should be considered in patients with early-onset stroke, especially with concomitant manifestations of inflammatory features or immunodeficiency. This case report extends the genotypic spectrum of ADA2 deficiency.
Sections du résumé
BACKGROUND
BACKGROUND
Adenosine deaminase 2 (ADA2) deficiency is an inherited autoinflammatory syndrome caused by a defect in the ADA2 gene. Most common manifestations include peripheral vasculopathy, early-onset stroke, immunodeficiency, and haematological manifestations. Patients with pathogenic variants that are more detrimental to ADA2's enzymatic function (e.g. frameshift) have been reported to be prone to developing hematological phenotype. We report here the case of a 13-year-old Caucasian girl with a novel frameshift variant in the ADA2 gene and a clinical phenotype of early-onset stroke.
CASE PRESENTATION
METHODS
The patient was admitted to hospital with complaints of weakness in her right arm, unilateral facial weakness and speech problems. Her initial laboratory workup was normal; however, magnetic resonance imaging of her brain confirmed acute/subacute ischaemic changes in the posterior limb of the left-sided internal capsule and in the apical part of the thalamus. She also had manifestations of immunodeficiency - recurrent skin infections and otitis, chronic Molluscum contagiosum infection in anamnesis and B cell deficiency with a low level of serum IgA. The patient's DNA was analysed and two pathogenic variants were identified in the ADA2 gene, confirming a diagnosis of adenosine deaminase 2 (ADA2) deficiency. While one of the variants (c.506G > A (p.Arg169Gln)) has been reported previously, the other one is a novel frameshift variant, namely, c.464del (p.Pro155Hisfs*29). The patient received stroke rehabilitation, which significantly improved her functional state. Tumour necrosis factor inhibitor and methotrexate treatment was commenced, and the patient has remained stable with no further ischaemic events.
CONCLUSIONS
CONCLUSIONS
Although rare, ADA2 deficiency should be considered in patients with early-onset stroke, especially with concomitant manifestations of inflammatory features or immunodeficiency. This case report extends the genotypic spectrum of ADA2 deficiency.
Identifiants
pubmed: 36528591
doi: 10.1186/s12969-022-00781-9
pii: 10.1186/s12969-022-00781-9
pmc: PMC9759365
doi:
Substances chimiques
Adenosine Deaminase
EC 3.5.4.4
Intercellular Signaling Peptides and Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
118Informations de copyright
© 2022. The Author(s).
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