The Challenge of Diagnosing SAVI: Case Studies

Area of Science:

• Genetics
• Immunology
• Pediatrics

Background:

• Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a rare type I interferonopathy.
• It results from heterozygous mutations in the transmembrane protein 173 (TMEM173) gene, presenting with neonatal systemic inflammation, vasculopathy, and lung disease.

Observation:

• Two male infants presented with recurrent skin abscesses, skin lesions, respiratory infections, and pulmonary fibrosis.
• Despite extensive workup, including genetic testing for other lung disease genes, SAVI was not diagnosed during their lifetimes.
• Both patients died from respiratory and circulatory failure.

Findings:

• Postmortem genetic analysis revealed TMEM173 gene mutations (c.463G>A, p.V155M in P1; c.461A>G, p.N154S in P2) in both patients, confirming a diagnosis of SAVI.
• These mutations were located in exon 5 of the TMEM173 gene.

Implications:

• This case series underscores the critical need to consider SAVI in infants presenting with systemic inflammation, chilblain-like lesions, and pulmonary fibrosis.
• TMEM173 gene analysis is crucial for diagnosing SAVI, even in retrospect, to improve awareness and potentially guide future therapeutic strategies.