Tricho-hepato-enteric syndrome (THE-S): two cases and review of the literature

Eur J Pediatr. 2015 Oct;174(10):1405-11. doi: 10.1007/s00431-015-2563-z.

Jin Ho Chong ¹, Saumya Shekhar Jamuar ², Christina Ong ³, Koh Cheng Thoon ⁴, Ee Shien Tan ⁵, Angeline Lai ⁶, Mark Koh Jean Aan ⁷, Wilson Lek Wen Tan ⁸, Roger Foo ⁹, Ene Choo Tan ¹⁰, Yu-Lung Lau ¹¹, Woei Kang Liew ¹²

Affiliations

1 Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. chong.jin.ho@kkh.com.sg.
2 Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. saumya.s.jamuar@kkh.com.sg.
3 Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. christina.ong@kkh.com.sg.
4 Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. thoon.koh.cheng@kkh.com.sg.
5 Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. tan.ee.shien@kkh.com.sg.
6 Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. angeline.lai.hm@kkh.com.sg.
7 Department of Dermatology, KK Women's and Children's Hospital, Singapore, Singapore. mark.koh.ja@kkh.com.sg.
8 Genome Institute of Singapore, Singapore, Singapore. wlwtan@gis.a-star.edu.sg.
9 Genome Institute of Singapore, Singapore, Singapore. mdcrfsy@nus.edu.sg.
10 KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore. tan.ene.choo@kkh.com.sg.
11 Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong, SAR, China. lauylung@hku.hk.
12 Department of Paediatric Subspecialties, KK Women's and Children's Hospital, Singapore, Singapore. Liew.Woei.Kang@kkh.com.sg.

PMID: 25976726 DOI: 10.1007/s00431-015-2563-z

Abstract

Tricho-hepato-enteric syndrome (THE-S) is characterized by severe infantile diarrhea, failure to thrive, dysmorphism, woolly hair, and immune or hepatic dysfunction. We report two cases of East Asian descent with THE-S who had remained undiagnosed despite extensive investigations but were diagnosed on whole exome Sequencing (WES). Both cases presented with chronic diarrhea, failure to thrive, and recurrent infections. Case 1 had posteriorly rotated low set ears, mild retrognathia, and fine curly hypopigmented hair. She was managed with prolonged total parenteral nutrition and intravenous immunoglobulin infusions. Case 2 had sparse coarse brown hair as well as multiple lentigines and café-au-lait macules. She was managed with amino acid-based formula. For both cases, routine investigations were inconclusive. WES in both cases showed biallelic truncating mutations in TTC37 (c.3507T>G;p.Y1169X and c.3601C>T;p.R1201X in case 1 and c.3507T>G;p.Y1169X and c.154G>T;p.E52X in case 2), suggesting a diagnosis of THE-S.

Conclusion: We present novel mutations in the TTC37 gene in two individuals of East Asian descent with the rare THE-S, detected by WES. Future identification of patients with THE-S and establishing genotype-phenotype correlations will aid in counseling the patients and their families.

What is known: • Tricho-Hepato-Enteric syndrome (THE-S) is characterized by severe infantile diarrhea, failure to thrive, dysmorphism, woolly hair, and immune or hepatic dysfunction. • Complex patients with diagnostic dilemmas undergo extensive investigations. What is New: • This is a report of novel mutations in TTC37 in individuals of East Asian descent. • Whole exome Sequencing (WES) can be useful in certain complex cases with diagnostic dilemmas.

Keywords

Chronic diarrhea; TTC37; Trichohepatoenteric syndrome; Whole exome sequencing; Woolly hair.

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