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Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiency

Haishao Yu1,2, Shuangzhu Lin3, Lin Li4

  • 1Department of Pediatrics, Yantai Yuhuangding Hospital, Shandong, China.

Frontiers in Genetics
|January 30, 2025
PubMed

Insights

This case highlights a rare genetic disorder, deficiency of adenosine deaminase 2 (DADA2), presenting with fever and stroke-like symptoms. Early diagnosis and treatment with etanercept led to significant improvement and prevented further attacks.

Area of Science:

  • Genetics
  • Immunology
  • Neurology

Background:

  • Deficiency of adenosine deaminase 2 (DADA2) is a rare genetic autoinflammatory disease.
  • It is caused by mutations in the ADA2 gene, leading to reduced ADA2 enzyme activity.
  • Clinical manifestations can include fever, vasculitis, and neurological events like stroke.

Observation:

  • A 2-year-old girl presented with intermittent fever, left limb weakness, and transient urticaria.
  • Brain MRI revealed multiple ischemic lesions, indicating systemic inflammation and vasculitis.
  • Genetic analysis identified compound heterozygous variants in the ADA2 gene, including a novel intronic variant (c.1082-7T>A).

Findings:

  • The novel intronic variant was confirmed to affect mRNA splicing, causing a frameshift and premature stop codon.
  • Enzyme activity assays showed a significant decrease in ADA2 activity.
  • The patient was diagnosed with DADA2 based on clinical presentation, genetic, and enzymatic findings.

Implications:

  • This case expands the known spectrum of ADA2 gene variants associated with DADA2.
  • It underscores the importance of genetic and enzymatic testing for diagnosing DADA2, especially in atypical presentations.
  • Treatment with etanercept demonstrated efficacy in managing DADA2 symptoms, preventing recurrent neurological events and fever.
Abstract

Keywords:
ADA2 geneCECR1 genechildrendeficiency of adenosine deaminase 2hemiplegia

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