# Case Report: Tricho-hepato-enteric syndrome in an infant presented with colorectal ulceration and severe respiratory superinfection

## TL;DR

This case report describes a rare genetic disorder in an infant that led to severe digestive and immune issues, resulting in early death.

## Contribution

The report highlights a fatal clinical course of THES in infancy with unique diagnostic and management challenges.

## Key findings

- THES can present with severe respiratory superinfection and early-onset ulcerative colitis in infants.
- Compound heterozygous TTC37 mutations were identified as the cause of THES in this case.
- Immunological and genetic analyses are essential for diagnosing THES in infants with systemic features.

## Abstract

Tricho-hepato-enteric syndrome (THES) is a rare genetic disorder characterized by early-onset intractable diarrhea, intrauterine growth retardation, hair abnormalities, and liver disease during early infancy. THES is often associated with combined immunodeficiency caused by defective interferon-γ production in T cells and hypogammaglobulinemia. However, very few cases of a severe clinical course in infancy have been reported.

Here, we report the case of a 2-month-old boy who presented with intractable diarrhea, growth retardation, and hair anomaly. Although fasting and central venous nutrition reduced stool frequency, effective weight gain was not achieved. A colonoscopy revealed multiple irregular ulcers without any cytomegalovirus (CMV)-positive cells. Nevertheless, CMV was detected in peripheral blood using a polymerase chain reaction, and the patient was initially treated with ganciclovir. However, this approach was not clinically effective. The second endoscopy revealed new colonic ulcers with mild active inflammation, and treatment with prednisolone was partially effective. The Immunological evaluation revealed no impaired findings, except for low blastogenesis in T cells. However, the patient developed severe progressive respiratory failure caused by superinfection with Pneumocystis jirovecii and CMV and died at 6 months of age. Clinical sequencing analysis identified compound heterozygous frameshift variants c.195dupA (p.A66Sfs*3) and c.3426dupA (p.A1143Sfs*4) in TTC37 (NM_014639.4), confirming the diagnosis of THES.

THES can have a fatal clinical course even during infancy. Detailed immunological and genetic analyses, in addition to endoscopic examination, are crucial for the definitive diagnosis and management of patients with very early-onset inflammatory bowel disease and inborn errors of immunity with systemic features.