We are reporting a case of neonatal diabetes mellitus, eczema andchronic diarrhea, suspected clinically to have ImmunodysregulationPolyendocrinopathy Enteropathy X-linked (IPEX) syndrome and the diagnosiswas confirmed by genetic testing. IPEX syndrome is a rare inherited X-linkedrecessive condition, causing life-threatening systemic autoimmune disorderwhich is characterized by immune dysregulation, polyendocrinopathy andenteropathy. The child who presented to our clinic at 11 months of age,had diabetic ketoacidosis at the age of 3 weeks, and was managed at thattime and then was started on multiple dose insulin injection regimen, alsohe had a history of recurrent episodes of eczematous dermatitis and chronicdiarrhea that started since early infancy. The rarity of this condition, mayhad led to delayed diagnosis and hence delayed definitive treatment – namelybone marrow transplant, which has variable outcomes. Immunosuppressivetreatment can be used, if bone marrow transplant is not feasible.
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1. Powell BR, Buist NR, Stenzel P. An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy. J Pediatr 1982; 100: 731-737.
2. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001; 27: 20-21.
3. Baud O, Goulet O, Canioni D, et al. Treatment of the immune dysregulation, polyendoccrinopathy, enteropathy, X linked syndrome (IPEX) by allogeneic bone marrow transplantation. N Engl J Med 2001; 344: 1758-1762.
4. Rubio-Cabezas O, Minton JAL, Caswell R, et al. Clinical heterogeneity in patients with FOXP3 mutations presenting with permanent neonatal diabetes. Diabetes Care 2009; 32: 111-116.
5. Moraes-Vasconcelos D, Costa-Carvalho BT, Torgerson TR, Ochs HD. Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED. J Clin Immunol 2008; 28(Suppl 1): S11-S19.
6. Torgerson TR. Regulatory T cells in human autoimmune diseases. Springer Semin Immunopathol 2006; 28: 63-76.
7. Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet 2002; 39: 537-545.
8. Savova R, Arshinkova M, Houghton J, et al. Clinical case of immune dysregulation, polyendocrinopaty, enteropathy, X-linked (IPEX) syndrome with severe immune deficiency and late onset of endocrinopathy and enteropathy. Case Rep Med 2014; 2014: 564926.
9. Bennett CL, Ochs HD. IPEX is a unique X-linked syndrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenomena. Curr Opin Pediatr 2001; 13: 533-538.
10. De Benedetti F, Insalaco A, Diamanti A, et al. Mechanistic associations of a mild phenotype of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome. Clin Gastroenterol Hepatol 2006; 4: 653-659.
11. Bacchetta R, Passerini L, Gambineri E, et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J Clin Invest 2006; 116: 1713-1722.
12. Gavin MA, Rasmussen JP, Fontenot JD, et al. Foxp3-dependent programmeo of regulatory T-cell differentiation. Nature 2007; 445: 771-775.
13. Wan YY, Flavell RA. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007; 445: 766-770.
14. Valencia X, Lipsky PE. CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases. Nat Clin Pract Rheumatol 2007; 3: 619-626.
15. Bin Dhuban K, Piccirillo CA. The immunological and genetic basis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Curr Opin Allergy Clin Immunol 2015; 15: 525-532.
16. Wildin RS, Ramsdell F, Peake J, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 2001; 27: 18-20.
17. Kobayashi I, Nakanishi M, Okano M, Sakiyama Y, Matsumoto S. Combination therapy with tacrolimus and betamethasone for a patient with X-linked autoimmune enteropathy. Eur J Pediatr 1995; 154: 594- 595.
18. Kobayashi I, Kawamura N, Okano M. A longterm survivor with the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. N Engl J Med 2001; 345: 999-1000.
19. Rao A, Kamani N, Filipovich A, et al. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning, Blood 2007; 109: 383-385.