{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:39:57Z","timestamp":1789000797079,"version":"build-2803163510"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trichohepatoenteric syndrome (THES), also known as phenotypic diarrhea or syndromic diarrhea, is a rare autosomal recessive genetic disorder caused by mutations in SKIC2 (THES-type 2) or SKIC3 (THES-type 1) and is characterized by early onset diarrhea, woolly brittle hair, facial dysmorphic features and liver disease. We report the case of a 24-month-old girl who presented with chronic diarrhea since the neonatal period along with intrauterine growth restriction (IUGR), developmental delay, dysmorphic features, congenital heart defects, liver disease, and recurrent infections. The diagnosis was made through whole-exome sequencing analysis, which detected a homozygous variant (c.4070del, p.Pro1357Leufs*10) in the SKIC3 gene. The patient required parenteral nutrition and was hospitalized for the first 10 months of life and then discharged on PN after showing improvement. She remained stable on PN after discharge despite a few admissions for central line infections. Recent follow-up at the age of 2 years revealed that she was stable on long-term parenteral nutrition and that she had advanced chronic liver disease.<\/jats:p>","DOI":"10.1186\/s12887-024-04924-7","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T07:02:36Z","timestamp":1720594956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Trichohepatoenteric syndrome type 1: expanding the clinical spectrum of THES type 1 due to a homozygous variant in the SKIC3 gene"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3669-0199","authenticated-orcid":false,"given":"Abdullah","family":"Alrammal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0765-2592","authenticated-orcid":false,"given":"Rashed","family":"Aljundi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2419-786X","authenticated-orcid":false,"given":"Sedra","family":"Abu Ghedda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buthaina Mustafa","family":"AlMurbati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"issue":"6","key":"4924_CR1","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1002\/humu.23418","volume":"39","author":"P Bourgeois","year":"2018","unstructured":"Bourgeois P, Esteve C, Chaix C, B\u00e9roud C, L\u00e9vy N, Fabre A, Badens C. Tricho-Hepato-Enteric syndrome mutation update: mutations spectrum of TTC37 and SKIV2L, clinical analysis and future prospects. Hum Mutat. 2018;39(6):774\u201389. https:\/\/doi.org\/10.1002\/humu.23418.","journal-title":"Hum Mutat"},{"key":"4924_CR2","doi-asserted-by":"publisher","unstructured":"Hu X, Hu W, Sun X, Chen L. (2022). Novel TTC37 mutations in a patient with Trichohepatoenteric syndrome: a case report and literature review. In Translational Pediatrics (Vol. 11, Issue 6, pp. 1050\u20131057). AME Publishing Company. https:\/\/doi.org\/10.21037\/tp-21-574.","DOI":"10.21037\/tp-21-574"},{"key":"4924_CR3","doi-asserted-by":"publisher","unstructured":"Alghamdi MS, Alsulimani EF, Almasrahi AM, Alsalmi KA. A case of mild trichohepatoenteric syndrome with new variant mutation in SKIV2L Gene: Case Report. Cureus.; 2021. https:\/\/doi.org\/10.7759\/cureus.19404.","DOI":"10.7759\/cureus.19404"},{"key":"4924_CR4","doi-asserted-by":"publisher","unstructured":"Bourgeois P, Coste ME, Roman C, Barlogis V, Badens C. (2017). Management of syndromic diarrhea\/tricho-hepato-enteric syndrome: A review of the literature. In Intractable and Rare Diseases Research (Vol. 6, Issue 3, pp. 152\u2013157). International Advancement Center for Medicine and Health Research. https:\/\/doi.org\/10.5582\/irdr.2017.01040.","DOI":"10.5582\/irdr.2017.01040"},{"key":"4924_CR5","doi-asserted-by":"publisher","unstructured":"Dorum S, Gorukmez O. (2021). Expanding the clinical spectrum in trichohepatoenteric syndrome. American Journal of Medical Genetics, Part A, 185(10), 2873\u20132877. https:\/\/doi.org\/10.1002\/ajmg.a.62354.","DOI":"10.1002\/ajmg.a.62354"},{"issue":"2","key":"4924_CR6","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1159\/000339896","volume":"3","author":"UH Kotecha","year":"2012","unstructured":"Kotecha UH, Movva S, Puri RD, Verma IC. Trichohepatoenteric syndrome: founder mutation in Asian indians. Mol Syndromol. 2012;3(2):89\u201393. https:\/\/doi.org\/10.1159\/000339896.","journal-title":"Mol Syndromol"},{"key":"4924_CR7","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63409","author":"KY Lee","year":"2023","unstructured":"Lee KY, Bremner R, Hartley J, Protheroe S, Haller W, Johnson T, Whyte L. Long term outcomes in children with trichohepatoenteric syndrome. Am J Med Genet Part A. 2023. https:\/\/doi.org\/10.1002\/ajmg.a.63409.","journal-title":"Am J Med Genet Part A"},{"key":"4924_CR8","doi-asserted-by":"publisher","first-page":"2050313","DOI":"10.1177\/2050313x18807795","volume":"6","author":"I Xinias","year":"2018","unstructured":"Xinias I, Mavroudi A, Mouselimis D, Tsarouchas A, Vasilaki K, Roilides I, Lacaille F, Giouleme O. Trichohepatoenteric syndrome: a rare mutation in SKIV2L gene in the first Balkan reported case. SAGE Open Med Case Rep. 2018;6:2050313. https:\/\/doi.org\/10.1177\/2050313x18807795.","journal-title":"SAGE Open Med Case Rep"},{"key":"4924_CR9","volume-title":"GeneReviews\u00ae [Internet]","author":"A Fabre","year":"2018","unstructured":"Fabre A, Bourgeois P, Chaix C, Bertaux K, Goulet O, Badens C, Trichohepatoenteric S. Jan 11. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 2018. 1993\u20132024. PMID: 29334452."},{"key":"4924_CR10","doi-asserted-by":"publisher","unstructured":"Gao J, Hu X, Hu W, Sun X, Chen L. (2022). Novel TTC37 mutations in a patient with Trichohepatoenteric syndrome: a case report and literature review. In Translational Pediatrics (Vol. 11, Issue 6, pp. 1050\u20131057). AME Publishing Company.https:\/\/doi.org\/10.21037\/tp-21-574.","DOI":"10.21037\/tp-21-574"},{"issue":"1","key":"4924_CR11","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1136\/archdischild-2013-304016","volume":"99","author":"A Fabre","year":"2014","unstructured":"Fabre A, Breton A, Coste ME, Colomb V, Dubern B, Lachaux A, Lemale J, Mancini J, Marinier E, Martinez-Vinson C, Peretti N, Perry A, Roquelaure B, Venaille A, Sarles J, Goulet O, Badens C. Syndromic (phenotypic) diarrhoea of infancy\/tricho-hepato-enteric syndrome. Arch Dis Child. 2014;99(1):35\u20138. https:\/\/doi.org\/10.1136\/archdischild-2013-304016. Epub 2013 Oct 9. PMID: 24108068.","journal-title":"Arch Dis Child"},{"issue":"1","key":"4924_CR12","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/ijd.13820","volume":"57","author":"PH Rambhia","year":"2018","unstructured":"Rambhia PH, Hanna R, Bergfeld WF. Graft versus host disease in a pediatric multiple organ transplant recipient with trichohepatoenteric syndrome \u2013 a unique case report. Int J Dermatol. 2018;57(1):89\u201391. https:\/\/doi.org\/10.1111\/ijd.13820.","journal-title":"Int J Dermatol"}],"container-title":["BMC Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-024-04924-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12887-024-04924-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-024-04924-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T07:04:44Z","timestamp":1720595084000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpediatr.biomedcentral.com\/articles\/10.1186\/s12887-024-04924-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,10]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4924"],"URL":"https:\/\/doi.org\/10.1186\/s12887-024-04924-7","relation":{},"ISSN":["1471-2431"],"issn-type":[{"value":"1471-2431","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,10]]},"assertion":[{"value":"23 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent was obtained from the individual(s) parents for the publication of any potentially identifiable images or data included in this article. The study is available upon request and was waived by the ethics committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Approval for this case report study was provided by the Ethics Review Board of Al Jalila Children\u2019s Speciality Hospital (serial number 920413405).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no conflicts of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"I hereby confirm that the manuscript is an original work that has not been published previously, nor is it currently under consideration for publication elsewhere.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Confirmation of the origin and exclusivity of publication"}}],"article-number":"444"}}