{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:09:04Z","timestamp":1788242944430,"version":"build-2803163510"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Trichohepatoenteric syndrome (THES) is a very rare disorder that is characterized by intractable congenital diarrhea, woolly hair, intrauterine growth restriction, facial dysmorphism, and short stature. Our knowledge of THES is limited due to the small number of reported cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Thirty patients diagnosed with THES, all molecularly confirmed by whole exome sequencing (WES) to have biallelic variants in\n                      <jats:italic toggle=\"yes\">TTC37<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">SKIV2L<\/jats:italic>\n                      , were included in the study. Clinical, biochemical, and nutritional phenotypes and outcome data were collected from all participants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The median age of THES patients was 3.7 years (0.9\u201323 years). Diarrhea and malnutrition were the most common clinical features (100%). Other common features included hair abnormalities (96%), skin hyperpigmentation (87%), facial dysmorphic abnormalities (73%), psychomotor retardation (57%), and hepatic abnormalities (30%). Twenty-five patients required parenteral nutrition (83%) with a mean duration of 13.34 months, and nearly half were eventually weaned off. Parenteral nutrition was associated with a poor prognosis. The vast majority of cases (89.6%) had biallelic variants in\n                      <jats:italic toggle=\"yes\">SKIV2L<\/jats:italic>\n                      , with biallelic variants in\n                      <jats:italic toggle=\"yes\">TTC37<\/jats:italic>\n                      accounting for the remaining cases. A total of seven variants were identified in\n                      <jats:italic toggle=\"yes\">TTC37<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 3) and\n                      <jats:italic toggle=\"yes\">SKIV2L<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 4). The underlying genotype influenced some phenotypic aspects, especially liver involvement, which was more common in\n                      <jats:italic toggle=\"yes\">TTC37<\/jats:italic>\n                      -related THES.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our data helps define the natural history of THES and provide clinical management guidelines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/sjg.sjg_200_21","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T08:11:49Z","timestamp":1629101509000},"page":"135-142","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":9,"title":["Tricho-hepato-enteric syndrome"],"prefix":"10.4103","volume":"28","author":[{"given":"Badr M.","family":"Alsaleem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Hasosah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna Basheer M.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maher M.","family":"Al Hatlani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz Helal","family":"Alanazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Al-Hussaini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali T.","family":"Asery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid A.","family":"Alghamdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhanad M.","family":"AlRuwaithi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musa Ali M.","family":"Khormi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Al Sarkhy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali S.","family":"Alshamrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-9-20240829","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1136\/adc.57.3.212","article-title":"Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: A new syndrome","volume":"57","author":"Stankler","year":"1982","journal-title":"Arch Dis Child"},{"key":"R2-9-20240829","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S0022-3476(94)70118-0","article-title":"Intractable infant diarrhea associated with phenotypic abnormalities and immunodeficiency","volume":"125","author":"Girault","year":"1994","journal-title":"J Pediatr"},{"key":"R3-9-20240829","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/(SICI)1096-8628(19970211)68:4<391::AID-AJMG3>3.0.CO;2-P","article-title":"Tricho-hepato-enteric syndrome: Further delineation of a distinct syndrome with neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies","volume":"68","author":"Verloes","year":"1997","journal-title":"Am J Med Genet"},{"key":"R4-9-20240829","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/ajmg.a.31583","article-title":"Tricho-hepato-enteric syndrome: A case of hemochromatosis with intractable diarrhea, dysmorphic features, and hair abnormality","volume":"143A","author":"Dweikat","year":"2007","journal-title":"Am J Med Genet A"},{"key":"R5-9-20240829","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/ajmg.a.31634","article-title":"Intractable diarrhea with \u201cphenotypic anomalies\u201c and tricho-hepato-enteric syndrome: Two names for the same disorder","volume":"143A","author":"Fabre","year":"2007","journal-title":"Am J Med Genet A"},{"key":"R6-9-20240829","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1750-1172-8-5","article-title":"Syndromic diarrhea\/Tricho-hepato-enteric syndrome","volume":"8","author":"Fabre","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"R7-9-20240829","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5582\/irdr.3.8","article-title":"Human Mendelian diseases related to abnormalities of the RNA exosome or its cofactors","volume":"3","author":"Fabre","year":"2014","journal-title":"Intractable Rare Dis Res"},{"key":"R8-9-20240829","doi-asserted-by":"crossref","first-page":"2398.e1","DOI":"10.1053\/j.gastro.2010.02.010","article-title":"Mutations in TTC37 cause trichohepatoenteric syndrome (phenotypic diarrhea of infancy)","volume":"138","author":"Hartley","year":"2010","journal-title":"Gastroenterology"},{"key":"R9-9-20240829","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/humu.21420","article-title":"Novel mutations in TTC37 associated with tricho-hepato-enteric syndrome","volume":"32","author":"Fabre","year":"2011","journal-title":"Hum Mutat"},{"key":"R10-9-20240829","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.ajhg.2012.02.009","article-title":"SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric syndrome","volume":"90","author":"Fabre","year":"2012","journal-title":"Am J Hum Genet"},{"key":"R11-9-20240829","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1136\/archdischild-2013-304016","article-title":"Syndromic (phenotypic) diarrhoea of infancy\/tricho-hepato-enteric syndrome","volume":"99","author":"Fabre","year":"2014","journal-title":"Arch Dis Child"},{"key":"R12-9-20240829","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1097\/MPG.0000000000000627","article-title":"Expanding phenotypic and allelic heterogeneity of tricho-hepato-enteric syndrome","volume":"60","author":"Monies","year":"2015","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R13-9-20240829","doi-asserted-by":"crossref","first-page":"e2918","DOI":"10.1097\/MD.0000000000002918","article-title":"Identifying mutations of the tetratricopeptide repeat domain 37 (TTC37) gene in infants with intractable diarrhea and a comparison of Asian and Non-Asian phenotype and genotype: A global case-report study of a well-defined syndrome with immunodeficiency","volume":"95","author":"Lee","year":"2016","journal-title":"Medicine (Baltimore"},{"key":"R14-9-20240829","doi-asserted-by":"crossref","first-page":"152","DOI":"10.5582\/irdr.2017.01040","article-title":"Management of syndromic diarrhea\/tricho-hepato-enteric syndrome: A review of the literature","volume":"6","author":"Fabre","year":"2017","journal-title":"Intractable Rare Dis Res"},{"key":"R15-9-20240829","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/humu.23418","article-title":"Tricho-Hepato-Enteric syndrome mutation update: Mutations spectrum of TTC37 and SKIV2L, clinical analysis and future prospects","volume":"39","author":"Bourgeois","year":"2018","journal-title":"Hum Mutat"},{"key":"R17-9-20240829","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.3389\/fimmu.2018.01036","article-title":"Combined immunodeficiency in patients with trichohepatoenteric syndrome","volume":"9","author":"V\u00e9ly","year":"2018","journal-title":"Front Immunol"},{"key":"R18-9-20240829","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12881-017-0388-5","article-title":"Exome sequencing identifies a novel TTC37 mutation in the first reported case of Trichohepatoenteric syndrome (THE-S) in South Africa","volume":"18","author":"Kinnear","year":"2017","journal-title":"BMC Med Genet"},{"key":"R19-9-20240829","doi-asserted-by":"crossref","first-page":"e8601","DOI":"10.1097\/MD.0000000000008601","article-title":"Tricho-hepato-enteric syndrome with novel SKIV2L gene mutations: A case report","volume":"96","author":"Hiejima","year":"2017","journal-title":"Medicine (Baltimore"},{"key":"R20-9-20240829","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.gene.2019.02.059","article-title":"Tricho-hepatic-enteric syndrome (THES) without intractable diarrhoea","volume":"699","author":"Poulton","year":"2019","journal-title":"Gene"},{"key":"R21-9-20240829","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.jpeds.2004.01.026","article-title":"\u201cSyndromic diarrhea\u201c may have better outcome than previously reported","volume":"144","author":"Barabino","year":"2004","journal-title":"J Pediatr"},{"key":"R22-9-20240829","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s13059-020-02053-9","article-title":"Analysis of transcript-deleterious variants in Mendelian disorders: Implications for RNA-based diagnostics","volume":"21","author":"Maddirevula","year":"2020","journal-title":"Genome Biol"},{"key":"R23-9-20240829","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/gim.2016.37","article-title":"Clinical genomics can facilitate countrywide estimation of autosomal recessive disease burden","volume":"18","author":"Abouelhoda","year":"2016","journal-title":"Genet Med"},{"key":"R24-9-20240829","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1097\/MPG.0b013e31825600c4","article-title":"A new genetic mutation in a patient with syndromic diarrhea and hepatoblastoma","volume":"57","author":"Bozzetti","year":"2013","journal-title":"J Pediatr Gastroenterol Nutr"}],"container-title":["Saudi Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/sjg.sjg_200_21","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:31:11Z","timestamp":1786735871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/sjg.sjg_200_21"}},"subtitle":["Retrospective multicenter experience in Saudi Arabia"],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.4103\/sjg.sjg_200_21","relation":{},"ISSN":["1319-3767"],"issn-type":[{"value":"1319-3767","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3]]}}}