Long term outcomes in children with trichohepatoenteric syndrome

Trichohepatoenteric syndrome (THES) is a rare autosomal recessive disorder caused by mutations in either TTC37 or SKIV2L, usually leading to congenital diarrhea as part of a multisystem disease. Here, we report on the natural history of the disease for the largest UK cohort of patients with THES from 1996 to 2020. We systematically reviewed the clinical records and pathological specimens of patients diagnosed with THES managed in a single tertiary pediatric gastroenterology unit. Between 1996 and 2020, 13 patients (7 female and 6 male) were diagnosed with THES either by mutation analysis or by clinical phenotype. Two patients died from complications of infection. All patients received parenteral nutrition (PN) of which six patients were weaned off PN. All patients had gastrointestinal tract inflammation on endoscopy. Almost half of the cohort were diagnosed with monogenic inflammatory bowel disease (IBD) by the age of 11 years, confirmed by endoscopic and histological findings. Protracted diarrhea causing intestinal failure improves with time in all patients with THES, but monogenic IBD develops in later childhood that is refractory to conventional IBD treatments. Respiratory issues contribute to significant morbidity and mortality, and good respiratory care is crucial to prevent comorbidity.