Enterocolitis with fulminate sepsis in a newborn with tricho-hepato-enteric syndrome: A case report

Abstract

Tricho-hepato-enteric syndrome is a rare autosomal recessive enteropathy that first presents as intractable diarrhea in neonates. Diarrhea persists throughout life and patients are dependent on parenteral nutrition for growth. Additional features include facial dysmorphism, trichorrhexis nodosa (woolly hair), intra-uterine growth restriction, hepatic disease, skin anomalies and a depressed immune system. Tricho-hepato-enteric syndrome is a life limiting disease with variability in its manifestations and severity. Mutations in two different genes, TTC37 or SKIV2L, cause the disorder. In this case report we present a neonate with a novel mutation in TTC37 that resulted in a severe phenotype associated with fulminate sepsis. The infant presented at one week of age with sudden onset of diarrhea and dehydration. Tricho-hepato-enteric syndrome was diagnosed by whole exome sequencing but was not initially considered because the infant lacked many of the diagnostic clinical features. Soon after presentation, the infant developed pneumoperitoneum and necrosis of entire bowel. The blood culture was positive for Clostridium perfringens. Autopsy showed bacteria in the parenchyma and vasculature of all major internal organs as well as within the bone marrow, connective tissue and skeletal muscle but there was minimal inflammatory response. The lack of migration of white blood cells to the sites of infection is likely due to the combined immunodeficiency reported in patients with tricho-hepato-enteric syndrome. This case expands our knowledge on the clinical features of tricho-hepato-enteric syndrome. Whole-exome sequencing was instrumental in making the diagnosis in an infant with an atypical presentation and should be considered early in neonates with congenital diarrhea.