Atypical Presentations of IPEX: Expect the Unexpected

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• Immune dysregulation, polyendocrinopathy, and enteropathy, X-linked (IPEX) syndrome is a rare monogenic autoimmune disorder.
• It is caused by mutations in the FOXP3 gene, a critical regulator of regulatory T cells (Tregs).
• Classical IPEX involves early-onset intractable diarrhea, type 1 diabetes, and eczema.

Purpose of the Study:

• To review and describe unusual clinical phenotypes of IPEX beyond the classical triad.
• To increase awareness of atypical IPEX presentations.
• To emphasize the importance of prompt diagnosis for effective treatment and improved quality of life.

Main Methods:

• Literature review of reported IPEX cases over the last 20 years.
• Analysis of clinical spectrum, including atypical presentations.
• Synthesis of information on diagnosis and treatment strategies.

Main Results:

• IPEX encompasses a broader clinical spectrum than previously recognized, including late-onset symptoms, single-organ involvement, and rare features like atrophic gastritis, interstitial lung disease, and nephropathy.
• Atypical presentations suggest that IPEX incidence may be underestimated.
• Immunosuppression can manage symptoms, but allogeneic hematopoietic stem cell transplantation remains the only definitive cure.

Conclusions:

• Recognizing atypical IPEX phenotypes is essential for accurate diagnosis and timely intervention.
• Prompt diagnosis improves management outcomes and patient quality of life.
• Further research into IPEX's diverse manifestations is warranted.