Approach to the patient with APS-1/APECED.
Taura Webb, Joseph Pechacek, Michail S Lionakis
✦ AI-curated · Sources linked
Case in brief
This article presents five cases of autoimmune polyendocrine syndrome type 1 (APS-1/APECED), a disorder caused by impaired immune tolerance and typically associated with biallelic AIRE variants. The cases illustrate a broad clinical spectrum, including non-endocrine manifestations that may precede hypoparathyroidism or adrenal insufficiency and delay recognition. Diagnostic challenges included limitations of standard genetic testing, with deep intronic and dominant-negative AIRE variants among the mechanisms considered. The report also discusses emerging understanding of interferon-γ-driven disease and targeted immunomodulatory approaches, including ruxolitinib.
What made this case unusual
The cases emphasize that non-endocrine features can precede classical endocrinopathies, and that APS-1 may involve deep intronic or dominant-negative AIRE variants not readily identified by standard genetic testing.
Diagnostic / clinical pearl
Consider APS-1 when compatible non-endocrine features occur, even before hypoparathyroidism or adrenal insufficiency; standard genetic testing may not detect all relevant AIRE variants.
Why it matters
Earlier recognition can support proactive surveillance and may enable timely consideration of disease-modifying treatment.