Tufting Enteropathy: A Review of Clinical and Histological Presentation, Etiology, Management, and Outcome

Abstract

Congenital tufting enteropathy (CTE), also named intestinal epithelial dysplasia, is a rare, autosomal recessive enteropathy with persistent and life-threatening intractable diarrhea early in life. Intractable diarrhea is present independent of breast or formula feeding. Most CTE patients require total parenteral nutrition (TPN), and in severe cases, small bowel transplantation is needed. In the last decade, we have seen remarkable progress in certain aspects, such as the pathogenesis and diagnostic methods of the disease. Rapidly developing molecular analysis techniques have improved the diagnostic methods for CTE and reduced invasive and expensive procedures. Mutations in the gene encoding human epithelial cell adhesion molecule (EpCAM) were identified in the typical form of CTE, which usually exhibits isolated refractory diarrhea. Moreover, the syndromic form of CTE features anal and choanal atresias as well as ophthalmologic signs, which are associated with mutations in the gene encoding Serine Peptidase Inhibitor Kunitz Type 2 (SPINT2). This article reviews CTE disease based on its clinical and histological presentation, etiology and pathogenesis, and management and outcome.

Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms

“…Moreover, CTE patients are also reported to have other signs or symptoms, including skeletal dysplasia [15], cholestatic liver disease, chronic arthritis [5,29], bone and dermatological abnormalities [16]. Arthritis is more common in patients with EPCAM mutations who have extra-intestinal manifestations, whereas ophthalmological symptoms and atresia are more common in patients with SPINT2 mutations [12]. These findings may help us in understanding the pathophysiology of this disease.…”

“…Although typically, no inflammatory cell infiltration is seen in CTE, some inflammatory infiltration can be found [13]. Just over 200 cases have been reported for this rare disease, and many of these are clinically heterogeneous [12]. The severity of this disease varies.…”

“…Nutrient malabsorption and intractable diarrhea lead infants to become irritable and develop dehydration as well as weight loss [21], ultimately resulting in impaired growth and failure to thrive [3,10]. Apart from intractable diarrhea, some CTE patients develop vomiting and abdominal distension [12,21]. Elevated osmolality, osmotic gap and quantitative fecal fat have been reported in CTE [20,21], and equivalent fecal loss of Na+ was found when compared to congenital sodium diarrhea [22].…”

“…Although Serine Peptidase Inhibitor Kunitz Type 2 (SPINT2) mutations have also been reported in a syndromic form of the disease, most CTE patients possess mutations in EPCAM [11]. Though not all patients are reported in the literature, a recent review suggests 74% of those reported have mutations in EPCAM, while 26% have mutations in SPINT2 [12].…”

Expansion of the ophthalmic phenotype of SPINT2‐related syndromic congenital sodium diarrhea

“…Common features of SCSD comprise congenital sodium diarrhea, choanal or anal atresia, hypertelorism, and corneal erosions. Before molecular analysis techniques became readily available, it was difficult to distinguish it from nonsyndromic congenital tufting enteropathy (CTE) caused by pathogenic variants in the EpCAM gene (Cai et al, 2020). Our patient is homozygous for a well‐established SPINT2 missense variant c.488A > G (p.Y163C).…”