ESPE Abstracts

Introduction: IPEX Syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) is characterized by mutations in the Forkhead BoxP3 (FOXP3) transcription factor, leading to autoimmunity in various organs starting in the perinatal period. This syndrome manifests with proliferative lesions in the thyroid gland, gastrointestinal system, skin, and other organs. We report a case of a 4-month-old male with neonatal diabetes, resistant thrombocytopenia, and atopic dermatitis, diagnosed with IPEX syndrome.

Case: A two-month-old male patient with neonatal diabetes was admitted to the PICU with fever, widespread petechial rashes, and conjunctival hemorrhage due to suspected meningococcemia. He was born at term weighing 2900 grams, with a history of third-degree consanguinity between his parents. He was diagnosed with neonatal diabetes on the ninth postnatal day following episodes of vomiting and poor general condition; he was managed on a basal-bolus insulin regimen, and his blood sugar profile was monitored by continuous glucose monitoring. Diagnostic tests for diabetes showed glucose: 299 mg/dL, c-peptide: <0.02 µg/L, positive anti-GAD, negative islet cell antibody, positive anti-insulin antibodies. At presentation, the patient exhibited the following measurements: length of 56.5 cm (-0.6 SD), weight of 5.2 kg (-0.48 SD), and head circumference of 38 cm (-1.47 SD). Clinical examination revealed widespread petechiae and ecchymoses on the limbs and trunk, bilateral conjunctival hemorrhage, and bilateral atopic dermatitis on the cheeks. Laboratory tests indicated a hemoglobin level of 7.2 g/dL, MCV of 94 fL, RDW of 20%, RBC count of 2.32 × 10^6/µL, platelet count of 17,000/µL, MPV of 11.8 fL, and WBC count of 8,250/µL, with microthrombocytes observed in the peripheral smear. No specific microorganisms were identified in cultures. During antibiotic treatment, the patient required several platelet replacements due to persistent thrombocytopenia. Treatments with intravenous immunoglobulin and corticosteroids successfully elevated the platelet count to 208,000/µL. Genetic analysis identified a likely pathogenic hemizygous FOXP3 gene c.542G>C variant. The patient is currently being evaluated for bone marrow transplantation.

Conclusion: IPEX syndrome is characterized by multi-organ involvement and endocrinopathy (such as neonatal diabetes and autoimmune thyroiditis) and presents with variable clinical manifestations depending on the mutation location. Persistent diarrhea resulting from enteropathy is the most common finding, seen in 97% of cases reported in the literature. Our case, lacking diarrhea, may represent a less frequently reported mutation. Even without diarrhea, IPEX syndrome should be considered in patients with neonatal diabetes mellitus presenting with thrombocytopenia and atopic dermatitis.

Keywords: Neonatal diabetes mellitus, thrombocytopenia, IPEX syndrome