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Sofia Bota1, Isabel Afonso2, Ana Isabel Cordeiro3, Conceição Neves3, Catherine Badens4,5, Alexandre Fabre5,6, João Farela Neves3,7

1 - Pediatric Department, Dona Estefânia Hospital, Central Lisbon Hospitalar Center, EPE. Lisbon, Portugal;
2 - Gastroenterology Unit, Dona Estefânia Hospital, Central Lisbon Hospitalar Center, EPE. Lisbon, Portugal;
3 - Primary Immunodeficiencies Unit, Dona Estefânia Hospital, Central Lisbon Hospitalar Center, EPE. Lisbon, Portugal;
4 - Laboratoire de Génétique Moléculaire, Hôpital d’enfants de la Timone, APHM, Marseille, France;
5 - Faculté de Médecine, Inserm UMRS 910, Aix-Marseille Université, Marseille, France;
6 - Service de Pédiatrie Multidisciplinaire, Hôpital d’enfants de la Timone, Marseille, France;
7 - Chronic Diseases Research Center, NOVA Medical School, Lisboa, Portugal

17th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2016), 21-24/09/2016, Barcelona, Spain (Poster)
ESPGHAN Young Investigators Forum, 21-24/09/2016, Bergen, Netherlands (Oral presentation)

Introdução : Syndromic diarrhea/tricho-hepato-enteric (SD/THE) syndrome is a rare disease caused by the alteration of two component of the SKI complex (TTC37 and SKIV2L). Its main features are an intractable diarrhea of infancy with non-specific abnormalities, associated to hair abnormalities (sparse, brittle, with trichorhexis nodosa), intrauterine growth restriction, facial dysmorphy (notably huge forehead and broad nasal root) and immune defect (often immunoglobulin defect). To date more than fifty cases have been published. The association of intractable diarrhea of infancy hair abnormalities is quite specific of SD/THE. 
Case report: The patient is a girl that was born prematurely at 33 weeks of gestational age, with a birth weight of 2050g (50P). She presented recurrent vomiting and failure to thrive. At the age of 2 months, a type 1 ileal atresia was diagnosed and an ileostomy was performed. She was kept on both parenteral and enteral nutrition. At the age of 5 months she developed bloody diarrhea despite the presence of an ileostomy. The colonic histology revealed inflammatory pseudo-polyps and glandular atrophy, thus allowing the diagnosis of VEO-IBD. She had severe and symptomatic hypogammaglobulinemia (recurrent respiratory infections). Her physical examination was notable for the presence of a big forehead and enamel dysplasia. The colitis worsened after the re-establishment of the intestinal tract. She also presented frequent flares of hepatitis that were self-limited. She started SCIg replacement at the age of 2 years old with dramatic reducing of the number infections and of the colonic inflammation. The association of enteropathy, facial dysmorphia, enamel dysplasia, hepatic abnormalities and hypogammaglobulinemia was evocative of SD/THE. However, the direct sequencing of TTC37 and SKIV2L was normal. A whole exome analysis performed showed compound mutation of TTC7A, which was confirmed by sanger sequencing.
Conclusão: TTC7A mutations have been previously linked to VEO-IBD. In this case, the patient also presented several manifestations of SD/THE. We confirm the huge variability of the phenotype associated with TTC7A abnormalities, which range from multiple intestinal atresia to chronic diarrhea associated with immune defects.

Palavras chave: TTC7A; Very-Early Onset Inflammatory Bowel Disease; Syndromic diarrhea/tricho-hepato-enteric; multiple intestinal atresia; chronic diarrhea