Congenital intestinal atresias with multiple episodes of sepsis A case report and review of literature Natalia Mandiá, MD a , Alejandro Pérez-Muñuzuri, MD, PhD a , Olalla López-Suárez, MD, PhD a , Carolina López-Sanguos, MD a , Adolfo Bautista-Casanovas, MD, PhD b , Mariá-Luz Couce, MD, PhD a, ∗ Abstract Introduction: Hereditary multiple intestinal atresia associated with severe combined immunodeficiency (MIA-SCID) is a very rare disease caused by deleterious mutations in the tetratricopeptide repeat domain-containing protein 7A gene TTC7A. It is characterized by intestinal obstruction, sepsis, and a poor prognosis. Insights into phenotype–genotype correlations could help to guide genetic counseling and increase our knowledge of the natural history of this disease. Case presentation: We report the case of a newborn in which his fetal magnetic resonance imaging showed jejunal atresia and microcolon and an abdominal x-ray at birth confirmed intestinal obstruction. The clinical course was complicated by multiple episodes of sepsis, and laboratory investigations showed SCID. The genetic analysis identified a homozygous c.53344_53347 mutation in the TTC7A gene compatible with MIA-SCID syndrome. The patient required 3 operations because of new intestinal atresias in the first months of life. She underwent bone marrow transplantation at 8 months of age but died of liver failure secondary to graft-versus-host disease. Conclusion: Immunologic assessment and genetic screening for TTC7A mutations are important in patients with MIA. Greater knowledge of the functions of the TTC7A protein will have important therapeutic implications for patients with MIA-SCID syndrome. Abbreviations: MIA = multiple intestinal atresia, TPN = total parenteral nutrition, SCID = combined immunodeficiency. Keywords: exome, gastrointestinal tract, neonatal sepsis, parenteral nutrition 1. Introduction Hereditary multiple intestinal atresia (MIA) (OMIM #243150) is a severe, very rare, congenital disease that involves multiples atretic injuries in diverse segments of the gastrointestinal tract, from the stomach to the rectum. [1,2] Approximately 10% to 15% of cases occur in association with severe combined immunodefi- ciency (SCID) and recurrent sepsis (MIA-SCID syndrome,). [3,4] According to a PubMed search, just 21 cases of MIA-SCID have been published [4–13] since the first case was described by Moreno et al [5] in 1990. All the cases to date have involved disruption of the epithelial barrier along the gastrointestinal tract, inversion of apicobasal polarity of the epithelial cells, and signs of intestinal epithelial apoptosis. Total parenteral nutrition (TPN) depen- dence and repeated episodes of sepsis are associated with a very poor prognosis and death occurs before the age of 2 years in 70% of patients. [4–13] In 2013, Samuels et al [6] identified the causative gene of MIA, the tetratricopeptide repeat domain-containing protein 7A gene TTC7A, through whole-exome sequencing. Since then, 20 mutations have been identified: skipping of exons 7, 12, and 18, p.L823P, p.Y105fs, p.K254fs, p.L823P, p.S678X, p.Q712X, p. L399P, p.Q277X, p.A832X, p.S539L, p.Y336X, p.L493fsX13, p. A558GfsX7, p.E71K, p.Q526X, and p.A832T. [7–13] However, the relation between TTC7A mutations and phenotype in patients with MIA-SCID syndrome remains to be clarified. We present a complicated case of MIA-SCID in an infant girl. The girl’s parents provided informed consent to the publication of this case. There were no other ethical requirements. 2. Case report A preterm female infant was born by vaginal delivery to healthy nonconsanguineous parents at 32 weeks of gestation. This was the first pregnancy of the mother, aged 35 years. The antenatal ultrasound at 6 months of gestation had shown a cystic malformation of the pelvis (25 94 cm) suggestive of dilated colon. Subsequent magnetic resonance imaging of the fetus confirmed jejunal atresia and microcolon. Chorionic villus sampling showed a normal female karyotype (46 XX). The birth weight was 1610 grams and the 10-minute Apgar score was 9. On admission, the patient had stable respiratory and Editor: N/A. Source of Support: Article-processing charge was covered by the Fundación IDIS-C012. The authors have no conflicts of interest to disclose. a Neonatal Unit, Department of Pediatrics, IDIS, CIBERER, b Pediatric Surgery Service, Deaprtment of Pediatrics, Clinical University Hospital of Santiago de Compostela, Santiago de Compostela University, IDIS, Spain. ∗ Correspondence: Mariá-Luz Couce, Neonatal Unit, Department of Pediatrics, Santiago de Compostela University Hospital, Travesía Choupana, s/n, 15706, Santiago de Compostela, Galicia, España (e-mail: maria.luz.couce.pico@sergas.es). Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC- ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Medicine (2018) 97:23(e10939) Received: 8 March 2018 / Accepted: 8 May 2018 http://dx.doi.org/10.1097/MD.0000000000010939 Clinical Case Report Medicine ® OPEN 1