Endocrine Abstracts

JOINT3412

Introduction: IPEX syndrome is a primary immunodeficiency caused by hemizygous mutations in the FOXP3, which encodes a key transcription factor essential for thymus-derived regulatory T cells to maintain immune tolerance. It is typically characterized by systemic autoimmunity beginning in the first year of life. This syndrome is defined by a triad of enteropathy, endocrinopathy, and eczematous dermatitis. Early diagnosis and treatment are crucial for preventing complications.

Case: A 4-year-2-month-old male patient was referred for hyperglycemia. Previous history revealed hematuria, proteinuria and thrombocytopenia at 2. 5 years. ANA and anti-dsDNA antibodies were positive, renal biopsy suggesting Class 5 lupus nephritis led to treatment with pulse steroids, intravenous immunoglobulin(IVIG), cyclophosphamide, azathioprine and hydroxychloroquine. In addition, recurrent pancytopenia, and later, recurrent thrombocytopenia and arthritis in the left knee was treated with MPZ, eventually he developed hyperglycemia for which insulin lispro was started. The patient was referred to our clinic for management of hyperglycemia. There was no history of consanguinity, however, two maternal uncles had a history of diabetes with onset at 10 years of age. The patient’s height and weight were normal, and systemic examinations were unremarkable. Investigations revealed elevated HbA1c, negative autoantibodies for diabetes, thyroid and celiac disease, normal liver, kidney, and thyroid functions, and anemia. Insulin glargine was added to the treatment. There was a progressive increase in HbA1c since the initiation of insulin(baseline: 4. 2%; 3^rd months: 5. 2%; 18^th: 10. 9%), and the family history of insulin-dependent diabetes in two uncles, thus genetic diabetes was suspected. Next-generation sequencing identified a hemizygous mutation in FOXP3. Further exploration of the uncles’ medical history revealed that one uncle was diagnosed with diabetes at age 11, and chronic diarrhea and microcytic anemia at age 14; while the other uncle developed diabetes at age 8, chronic diarrhea at age 11, thrombocytopenia at age 15, and adrenal insufficiency at age 18. Genetic testing confirmed the FOXP3 hemizygous mutation in the uncles, heterozygous in the mother. IVIG and fluconazole prophylaxis were initiated. High-resolution HLA samples were sent for the patient and siblings to assess suitability for HSCT.

Conclusion: IPEX syndrome presents with neonatal diabetes as well as early-onset enteropathy and eczema. However, it may have an atypical presentation, and should be considered in cases of diabetes of unknown etiology, especially associated with other autoimmune disorders, even when onset is after the first year of life, and is not accompanied by enteropathy/eczema.

Keywords: Autoimmune polyendocrinopathy, diabetes, nephropathy, arthritis, thrombocytopenia