Abstract
The syndromic diarrhea/trichohepatoenteric syndrome (SD/THE) is a rare and multi-system genetic disorder caused by mutation in SKIV2L or in TTC37, two genes encoding subunits of the putative human SKI complex involved in RNA degradation. The main features are intractable diarrhea of infancy, hair abnormalities, facial dysmorphism, and intrauterine growth restriction. Immunologically this syndrome is associated with a hypogammaglobulinemia leading to an immunoglobulin supplementation. Our immune evaluation of a large French cohort of SD/THE patient revealed several immunological defects. First, switched memory B lymphocytes count is very low. Second, IFN-γ production by T and NK cells is impaired and associated with a reduced degranulation of NK cells. Third, T cell proliferation was abnormal in 3/6 TTC37-mutated patients. These three patients present with severe EBV infection and a transient hemophagocytosis which may be related to these immunological defects. Moreover, an immunological screening of patients with clinical features of SD/THE could facilitate both diagnosis and therapeutic management of these patients.
Highlights
Syndromic diarrhea/trichohepatoenteric syndrome (SD/THE) was initially described by Girault et al in 1994 [1]
We collected immunological data of nine patients with SD/THE syndrome caused by mutations of either tetratricopeptide repeat domain-containing protein 37 (TTC37) or SKIV2L which is a large cohort regarding this rare deficiency
All patients presented with a classical SD/THE phenotype: intractable diarrhea of infancy beginning at a median age of 31 day (0–335), need for a parenteral nutrition, hair abnormalities, and trichorhexis nodosa (8/9)
Summary
Syndromic diarrhea/trichohepatoenteric syndrome (SD/THE) was initially described by Girault et al in 1994 [1]. It is a severe and rare disorder that is characterized by intractable diarrhea, facial and hair abnormalities, intrauterine growth retardation, skin abnormalities, liver disease, and less frequently congenital cardiac defects and platelet anomaly [2]. TTC37 and SKIV2L are both components of the superkiller (SKI) complex [3]. The superkiller complex is a cofactor of the cytosolic exosome, which is involved in the degradation of aberrant mRNA molecules [4]. Immunological defects such as low serum concentration of immunoglobulins and decreased or absent antibody responses to vaccination have been reported [2, 5, 6]
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