Purpose of review: To update on the molecular and cellular basis of multiple intestinal atresia (MIA).

Recent findings: Mutations of the tetratricopeptide repeat domain 7A gene have been identified in patients with MIA and other related disorders, including MIA associated with combined immunodeficiency and very early onset inflammatory bowel disease with apoptotic enterocolitis. Pathological findings in patients with MIA and MIA associated with combined immunodeficiency include abnormalities of enterocyte apicobasal polarity, increased apoptosis of intestinal cells, decreased proliferation of intestinal crypts, and defects of thymic architecture associated with lymphoid depletion. Dysregulated RhoA signaling and defective expression of phosphatidylinositol 4-kinase IIIα represent biochemical cellular hallmarks of the disease.

Summary: The study of patients with MIA and related disorders has established that tetratricopeptide repeat domain 7A plays a critical role in intestinal and immune homeostasis. Identification of biochemical defects may pave the way to novel pharmacological interventions for this group of severe congenital disorders.