Biallelic mutations in tetratricopeptide repeat domain 7A (TTC7A) gene have been shown to cause several overlapping clinical phenotypes in 56 patients worldwide. TTC7A is key factor to bridge the process of both immune system and digestive tract development. Most patients presented with multiple intestinal atresia (MIA) isolated or in association with immunodeficiency.
Here we present a 12-years-old female patient of Slavic origin (Belarus) with EBV positive Hodgkin lymphoma, bronchiectatic and celiac disease with biallelic mutations of the TTC7A gene.
A 8-year-old girl, born to non-consanguineous Belarus parents, presented with chronic obstructive pulmonary disease, multiple bronchiectasias due to repeated pneumonias and bronchitis, was hospitalized for detailed immunologic evaluations. The patient had low T cell (CD3+-470 cells/µL) with expansion of TCRgd T cells, accompanying with diminished numbers of recent thymic emigrants (CD4+CD45RA+CD31+-2.8%), with minor abnormalities in TCRVb repertoire. Humoral abnormalities included low level of IgA (0.03g/L) and diminished percentage of naïve (CD19+CD27-IgD+) B cells (30.8%).
In the age of 10 years generalized lymphadenopathy appeared and classic EBV positive Hodgkin Lymphoma Lymphocyte-rich CD20-negative was established on a resected lymph node. Treatment (2-OPPA; 2-COPP) was complicated with severe mucositis and esophagitis. After treatment patient suffered from lung insufficiency, celiacia (anti-gliadin Ab) and failure to thrive. Accidentally, patient died due to food aspiration at the age of 12 years and later found to have compound heterozygous mutations in TTC7A (p.K606R and p.S672P).
To our knowledge, this is the first case of a potential association between TTC37A mutation and lymphoma development.