Abstracts Interdisciplinary

Background:TTC7A-deficiency is a rare hereditary condition characterized by combined immunodeficiency with multiple intestinal atresias presenting in heterogenous degrees of severity [1] and is drawn back to consanguinity [2].The genetic disorder leads to disrupted and inverse construction of the apicobasal polarity in enterocytes as shown in intestinal organoids, derived from TTC7A-patients [3].The defect is also associated with a very early onset of inflammatory bowel disease [4].Immunodeficiency can be explained by inappropriate activation of the Rho-kinase and impairment of the actin cytoskeleton dynamic, resulting in modified proliferation, adhesion, and migratory capacities of the lymphocytes [5].The prognosis is fatal in approximately two thirds of the cases and treatment is based on palliative concepts [6, 7].Treatment options are limited, e.g., intestinal transplantation, as patients with multiple atresia and immunodeficiency are predisposed to develop severe Graft vs. Host disease [8].Therefore, unravelling of new signaling pathways in the pathogenesis are of great importance to optimize the use of remaining therapeutic options.In vitro treatment by pharmacological inhibition of the Rho-kinase has shown to be effective [3].The objective of this case report is to highlight treatment difficulties in the genetic disorder of TTC7A-deficiency and to review the recent understanding of the pathogenesis. Materials and methods:A male patient with prenatally suspected intestinal atresia underwent comprehensive assessment.The interdisciplinary evaluation included departments of human genetics, immunology, cardiology, neurology, radiology, pathology, neonatal intensive care medicine, and pediatric surgery at the University Medical Center Hamburg-Eppendorf.Literature was reviewed regarding the recent understanding of pathogenesis and treatment opportunities in patients with TTC7A-deficiency. Results:The study involved a male neonate with prepartal suspicion of intestinal atresia, characterized by a singular gastric bubble and an otherwise airless abdomen.Genomic analysis confirmed a homozygous TTC7A-deficiency (Q82.8Combined Immunodeficiency-Enteropathy Spectrum).Born spontaneously at 37+2 weeks, he was immediately admitted to the neonatal intensive care unit.Both sonographic and Xray examinations corroborated the suspicion of intestinal atresia, with the presence of a singular gastric bubble and a mostly airless abdomen.Following his birth, the patient received treatment involving gastric tube placement and total parenteral nutrition.Cerebral sonography showed no abnormalities, but echocardiography revealed a narrow aortic arch, a patent foramen ovale, and a patent ductus arteriosus.Immunological analysis indicated cytotoxic T-cell deficiency, reduced memory B-cells, and a disproportionate reduction in regulatory T-cells during T-cell differentiation.Surgical intervention was performed on the second day of life with the goal of restoring intestinal continuity.An exploratory laparotomy uncovered multiple intestinal atresias, totaling > 30, which included pyloric atresia, duodenal atresia, multiple jejunal and ileal atresias, and colonic atresia.Surgical procedures included pylorotomy and duodeno-jejunostomy, jejuno-jejunal bypass, Meckel's diverticulum resection, and creation of a descendostomy.Histological examination of Meckel's diverticulum showed inflammatory changes, mucosal edema, hemorrhages, but no dysplasia or malignancy.Although gastric distension improved postoperatively, the gastric tube still drained significant amounts, and there was a lack of peristalsis.Consequently, on the 16th day of life, a second laparotomy was performed, which involved scarred gastroduodenostomy dilatation, pylorus re-bypass anastomosis, jejunal re-anastomosis via jejuno-jejunostomy, and the creation of a double-barreled jejunostoma.