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. |
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Abbreviations
- CID:
-
Combined immunodeficiency
- CMV PCR:
-
Cytomegalovirus
- HSCT:
-
Hematopoietic stem cell transplant
- IVIG infusions:
-
intravenous immunoglobulin
- TPN:
-
Total parenteral nutrition
- THE-S:
-
Tricho-hepato-enteric syndrome
- WES:
-
Whole exome sequencing
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Acknowledgments
For Case 1, we would like to acknowledge Hong Kong Health and Medical Research Fund (HMRF 01120846 to Lau YL and Yang WL) and The Hong Kong Society for the Relief of Disabled Children and Children’s Cancer Foundation of Hong Kong (to Lau YL) for their support. For Case 2, we would like to acknowledge the research funding sources, KNMRCCGRC001 and KNMRCCGSF4-2 from NMRC, MOH as well as Agency for Science, Technology and Research (A*STAR), Biomedical Research Council. In addition, we would like to acknowledge Pamela Lee, Chan KW, Yang WL, The University of Hong Kong, for data analysis for Case 1; Dr Asif Javed, Genome Institute of Singapore, for his help with Phen-Gen analysis for Case 2, and Dr Maggie Brett, KK Women’s and Children’s Hospital, for Sanger validation of the variants detected in the two cases as well as testing the parents for carrier status.
Author’s contributions
JHC, SSJ, and WKL wrote the initial draft of the manuscript. Each author listed on the manuscript has reviewed the manuscript, approved the submission of this version of the manuscript, and takes full responsibility for the manuscript. All the clinicians (JHC, SSJ, MJAK, EST, AL, CO, KCT, YLL, WKL) were important in data acquisition and interpretation of these cases. The laboratory staff (WLWT, RF, ECT) were involved in data analysis. These two patients had complicated courses that required input from multiple authors.
Ethical statement
This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent is obtained from parents of the cases described.
Conflict of interest
The authors do not have a financial relationship with the organizations that sponsored the study.
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Communicated by Beat Steinmann
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Chong, J.H., Jamuar, S.S., Ong, C. et al. Tricho-hepato-enteric syndrome (THE-S): two cases and review of the literature. Eur J Pediatr 174, 1405–1411 (2015). https://doi.org/10.1007/s00431-015-2563-z
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DOI: https://doi.org/10.1007/s00431-015-2563-z