Background: IPEX (OMIM #304790) is a rare and fatal, X-linked immune dysregulatory disorder caused by mutation in transcription factor FOXP3 that result in either quantitative or functional deficiencies of Tregs causing autoimmune disease and allergic inflammation. HSCT is the only curative therapy available for IPEX patients.
Objective: Presented boy was born at 38th GW with birth weight 3380 g and birth length 50 cm. Three maternal brothers died in early infancy due to malabsorption. At the age of 6 weeks the patient developed Type 1 diabetes (T1D) with typical clinical and laboratory presentation (glycaemia 38 mmol/l, severe ketoacidosis and extremely high GAD antibodies >120 kIU/l). Subsequently he developed atopic dermatitis and progressive failure to thrive due to diarrhea. Immunosuppressive treatment with glucocorticoids was ineffective. At the age of 3 months he underwent HSCT from an unrelated HLA-matched donor. The HSCT course was uncomplicated, the outcome was favorable: gastrointestinal and skin symptoms fully resolved, the boy is fed orally and thriving well. C-peptide remained however undetectable (<3.33 pmol/l), insulin treatment could not be stopped. Nowadays, at the age of 7 months is the patients T1D well-controlled by CSII (HbA1c 45 mmol/mol) with daily insulin requirements of 0.63 IU/kg.
Method and results: Direct sequencing of FOXP3 gene revealed a novel c.721T>C (S241P) mutation in proband, his mother and sisters. The quantity of the patients Tregs was in normal range (9.0%), but in immunosuppressive assay his Tregs failed to suppresses proliferation of effector T cells if compared to healthy controls.
Conclusion: We describe a previously unreported c.721T>C (S241P) mutation in FOXP3 gene. To our knowledge we reported the youngest patient with IPEX who underwent successful HSCT. We suggest that an early genetic diagnosis followed by an early HSCT offers the greatest potential to correct the disease process and thereby minimize end-organ damage.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology