title: Tricho-hepato-enteric syndrome (THE-S): two cases and review of the literature.
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  • 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.
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. chong.jin.ho@kkh.com.sg.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Chong
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. saumya.s.jamuar@kkh.com.sg.
authors.forename: Saumya Shekhar
authors.initials: SS
authors.lastname: Jamuar
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. christina.ong@kkh.com.sg.
authors.forename: Christina
authors.initials: C
authors.lastname: Ong
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. thoon.koh.cheng@kkh.com.sg.
authors.forename: Koh Cheng
authors.initials: KC
authors.lastname: Thoon
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. tan.ee.shien@kkh.com.sg.
authors.forename: Ee Shien
authors.initials: ES
authors.lastname: Tan
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Rd, Singapore, 229899, Singapore. angeline.lai.hm@kkh.com.sg.
authors.forename: Angeline
authors.initials: A
authors.lastname: Lai
authors.affiliation: Department of Dermatology, KK Women's and Children's Hospital, Singapore, Singapore. mark.koh.ja@kkh.com.sg.
authors.forename: Mark Koh Jean
authors.initials: MK
authors.lastname: Aan
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore. wlwtan@gis.a-star.edu.sg.
authors.forename: Wilson Lek Wen
authors.initials: WL
authors.lastname: Tan
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore. mdcrfsy@nus.edu.sg.
authors.forename: Roger
authors.initials: R
authors.lastname: Foo
authors.affiliation: KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore. tan.ene.choo@kkh.com.sg.
authors.forename: Ene Choo
authors.initials: EC
authors.lastname: Tan
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong, SAR, China. lauylung@hku.hk.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Department of Paediatric Subspecialties, KK Women's and Children's Hospital, Singapore, Singapore. Liew.Woei.Kang@kkh.com.sg.
authors.forename: Woei Kang
authors.initials: WK
authors.lastname: Liew
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D003968:Diarrhea, Infantile / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D019066:Facies; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005820:Genetic Testing; D006201:Hair Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation
chemical_list: D002352:Carrier Proteins; C550452:TTC37 protein, human; D004247:DNA
keywords: Chronic diarrhea; TTC37; Trichohepatoenteric syndrome; Whole exome sequencing; Woolly hair