Publication Date

10-2024

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Abstract

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare inborn error of immunity. It affects about one in every 1.6 million people. It is caused by mutations in the forkhead box P3 (FOXP3) gene on chromosome Xp11.23. FOXP3 is a vital regulator of T cell development and function. Dysfunctional FOXP3 allows the hyperactivation of T cells, resulting in skin rash, enteropathy, diabetes, thyroiditis, hemolytic anemia, and thrombocytopenia. The classic clinical presentation is intractable diarrhea, growth problems, dermatitis, and autoimmune endocrinopathy. Case Description: A 4-week-old male was transferred to our hospital’s NICU due to respiratory distress and feeding difficulties. Neurology was consulted due to hypotonia and swallowing difficulties. Neurology recommended genetic testing. Exome sequencing identified a hemizygous pathogenic variant in FOXP3, consistent with a diagnosis of IPEX syndrome. Immunology, Endocrine, Dermatology and GI teams were consulted. The transplant team was involved. Immune workup was normal including normal FOXP3 protein expression in the Treg cell. He had myeloablative chemotherapy followed by matched unrelated donor stem cell transplant at the age of 4 months. He was discharged from hospital at the age of 6 months. Discussion: IPEX syndrome should be considered in young males with severe intractable diarrhea and other autoimmune endocrinopathies especially Insulin dependent diabetes mellitus (IDDM). Sequencing of the FOXP3 gene should always be carried out to look for mutations even in the face of normal FOXP3 protein expression in the Treg cell. A timely diagnosis is essential to offer HSCT in this potentially fatal disorder.

Disciplines

Allergy and Immunology

Notes

Presented at the 2024 American College of Allergy, Asthma & Immunology's Annual Scientific Meeting; Boston, Massachusetts; Oct 24-28, 2024.

An Early Successful Hematopoietic Stem Cell Transplant (Hsct) For A Boy With Ipex Syndrome

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