ESPE Abstracts

Background: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare and life-threatening primary immunodeficiency characterized by widespread autoimmunity. Mutations in the FOXP3 gene have been identified as the cause for IPEX syndrome.

Objective and hypotheses: To describe clinical characteristics and genetic finding in the first Vietnamese patient with mutation of FOXP3 gene.

Method: Clinical features, biochemical finding, mutation analysis in a 12 day-old-boy were studied. Based on analysis of a 12 day-old-boy’s clinical symptoms associated with biochemical examination, the diagnosis of IPEX was therefore confirmed. Genomic DNAs were extracted from peripheral blood leukocytes of proband and her parents with their informed consent for genetic studies. Analysis of the coding regions and conserved splice sites of the KCNJ11, ABCC8, INS, INSR, EIF2AK3, FOXP3, GATA4, GATA6, GCK, GLIS3, HNF1B, IER3IP1, PDX1, PTF1A, NEUROD1, NEUROG3, RFX6, SLC2A2, SLC19A2, WFS1 and ZFP57 genes was performed using targeted next generation sequencing. Mutation in exon 11 of FOXP3 was confirmed using Sanger sequencing.

Results: The patient had gestation age of 41 weeks, birth weight of 2400 g. He was admitted with prolong jaundice and suspected hypothyroidism in the results of newborn screening. On admission, he presented with diarrhea, jaundice, vomit, dehydration. After one day, he presented with the features of diabetic ketoacidosis with pH of 6.95; HCO₃⁻ of 1.5 mmol/l; BE of −28.9 mmol/l; Investigation showed: blood glucose level 91.31 mmol/l; HbA1C 3.5%; total bilirubin level 274.4 μmol/l; direct bilirubin level 18.17 μmol/l; AST 40.6 U/l; ALT 18.4 U/l; T₃ 0.4 nmol/l; T₄ 24.39 nmol/l; TSH 764.2 mUI/ml, urea 28.14 mmol/l; creatinine 179 μmol/l; Na⁺ 164 mmol/l, K⁺ 4.7 mmol/l, Cl⁻ 146 mmol/l. WBC 4.97 G/l, NEU 3.89 G/l, LYM 0.63 G/l. Sanger sequencing analysis showed hemizygous for a novel FOXP3 missense mutation, p.Pro378Leu from affected mother. He was treated with insulin infusion, adjustment of electrolyte and renal failure.

Conclusion: We reported a classical case of IPEX syndrome in a boy with severe DKA and hypothyroidism in the second week of age. The identification of a FOXP3 mutation in this family was important to predict prognosis for the child and risk for future offspring and enabled prenatal diagnosis.