TTC7A deficiency: A retrospective international study on treatment and outcomes from the Inborn Errors Working Party of EBMT.

Tetratricopeptide repeat domain 7A (TTC7A) deficiency is a primary immunodeficiency due to mutations in the TTC7A gene. It causes intestinal disease and a poorly characterized immunodeficiency, with poor long-term survival. We describe the clinical and immunological characteristics, management, and outcomes of an international cohort of patients with genetically confirmed TTC7A deficiency. Data from 61 patients from 13 countries were retrospectively analyzed. Overall survival was 64% (median follow-up 4.2 years), significantly higher in the inflammatory bowel disease than in the hereditary multiple intestinal atresia group (80 vs. 48%, P < 0.05). Infections represent the leading cause of death. Allogeneic stem cell transplantation was performed in 16 patients to correct the immunodeficiency but was associated with a significant transplant-related mortality (44%). Solid organ transplantation of the small bowel remains exceptionally rare (two patients). Malignancy/autoimmune disorders developed in 4 (6.5%) and 17 (28%) patients, respectively. TTC7A remains difficult to treat, and prognosis is dismal for affected patients. Further understanding of the disease mechanisms and development of innovative treatment approaches are required.