Novel mutations in a patient with Trichohepatoenteric syndrome: a case report and literature review.

Background: Trichohepatoenteric syndrome (THES) is a rare autosomal recessive genetic disease caused by pathogenic mutations in or gene. The presentation is variable, including intractable diarrhea, woolly hair abnormality, immune dysfunction, intrauterine growth restriction (IUGR), facial dysmorphism, and sometimes liver and skin abnormalities. Although four Chinese children affected with THES syndrome 1 have been described in Singapore, Taiwan (China) and Malaysia, to our knowledge, this is the first report of a patient with THES in Mainland China, harboring classical platelets features, clinical course, and novel mutations in gene.

Case Description: The male infant had symmetrical IUGR, and was born at 37 weeks with a birth weight of 1,480 g. He presented with feeding difficulties and vomiting from the 12 day after birth during the stay in neonatal intensive care unit, and had excessive diarrhea from the 21st day after birth. From the 35 day after birth, even slightly hypotonic oral rehydration solution caused watery stools. The blood glucose level was lower than 3.3 mmol/L even when the glucose infusion rate was up to 14 mg/kg/min on the parenteral alone, which has not been reported in previous literature. Normal α-granules were observed occasionally in THES platelets. Whole-exome sequencing analysis identified compound heterozygous mutations (c.4130C > G: p.S1377X) and (Exon11-13 del) in the gene, which had been inherited from his father and mother, respectively. To our knowledge, the above mutations have not been described in any database or previous literature. Total parenteral nutrition was employed as mainstay of therapy, and hydrocortisone (1 mg/kg/dose, every 4 hours) was used to maintain blood glucose levels. The patient's final prognosis was poor after discharged from the hospital.

Conclusions: This case presented with mild platelet abnormality and intractable hypoglycemia, which extends the known mutation and phenotype of THES. The clinical features of Chinese patient are consistent with other ethnicity. Molecular diagnosis is useful for patients with unexplained intractable diarrhea, which puts an end to a long diagnostic odyssey.