Tricho-hepato-enteric syndrome: Retrospective multicenter experience in Saudi Arabia

Area of Science:

• Genetics
• Pediatrics
• Gastroenterology

Background:

• Trichohepatoenteric syndrome (THES) is a rare genetic disorder characterized by severe congenital diarrhea, hair abnormalities, and growth issues.
• Limited data exists on the natural history and genetic basis of THES due to its rarity.

Purpose of the Study:

• To characterize the clinical phenotypes, genetic variants, and outcomes of Trichohepatoenteric syndrome (THES).
• To establish clinical management guidelines for THES based on a cohort study.

Main Methods:

• Whole exome sequencing (WES) was used to identify biallelic variants in TTC37 or SKIV2L in 30 diagnosed THES patients.
• Clinical, biochemical, nutritional, and outcome data were collected and analyzed for all participants.

Main Results:

• Diarrhea and malnutrition were universal (100%) in the 30 THES patients, followed by hair abnormalities (96%) and skin hyperpigmentation (87%).
• Biallelic variants in SKIV2L accounted for 89.6% of cases, while TTC37 variants were found in the remainder. Genotype influenced liver involvement.
• Parenteral nutrition was required in 83% of patients, and its use was associated with a poorer prognosis.

Conclusions:

• This study defines the natural history of Trichohepatoenteric syndrome (THES) in a cohort of 30 patients.
• The findings provide crucial data for developing clinical management guidelines for THES.