{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:37:54Z","timestamp":1789180674861,"version":"build-2803163510"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Syndromic diarrhea\/Tricho-hepato-enteric syndrome (SD\/THE) is a rare and severe bowel disorder caused by mutation in <jats:italic>SKIV2L<\/jats:italic> or in <jats:italic>TTC37<\/jats:italic>, 2 genes encoding subunits of the putative human SKI complex. The estimated prevalence is 1\/1,000,000 births and the transmission is autosomal recessive. The classical form is characterized by 5 clinical signs: intractable diarrhea of infancy beginning in the first month of life, usually leading to failure to thrive and requiring parenteral nutrition; facial dysmorphism characterised by prominent forehead and cheeks, broad nasal root and hypertelorism; hair abnormalities described as woolly and easily removable; immune disorders resulting from defective antibody production; intrauterine growth restriction. The aetiology is a defect in <jats:italic>TTC37<\/jats:italic>, a TPR containing protein, or in the RNA helicase <jats:italic>SKIV2L<\/jats:italic>, both constituting the putative human ski complex. The ski complex is a heterotetrameric cofactor of the cytoplasmic RNA exosome which ensures aberrants mRNAs decay. The diagnosis SD\/THE is initially based on clinical findings and confirmed by direct sequencing of <jats:italic>TTC37<\/jats:italic> and <jats:italic>SKIV2L<\/jats:italic>. Differential diagnosis with the other causes of intractable diarrhea is easily performed by pathologic investigations. During their clinical course, most of the children require parenteral nutrition and often immunoglobulin supplementation. With time, some of them can be weaned off parenteral nutrition and immunoglobulin supplementation. The prognosis depends on the management and is largely related to the occurrence of parenteral nutrition complications or infections. Even with optimal management, most of the children seem to experience failure to thrive and final short stature. Mild mental retardation is observed in half of the cases.<\/jats:p>\n          <jats:p>\n            <jats:bold>Abstract in French<\/jats:bold>\n          <\/jats:p>\n          <jats:p>Les diarrh\u00e9es syndromiques ou syndrome tricho-hepato-enterique (SD\/THE) sont un syndrome rare et s\u00e9v\u00e8re dont l\u2019incidence est estim\u00e9e \u00e0 1 cas pour 1 million de naissances et la transmission autosomique r\u00e9cessive. La forme typique associe 5 signes cliniques: une diarrh\u00e9e grave rebelle n\u00e9cessitant dans la majorit\u00e9 des cas une nutrition parent\u00e9rale du fait de la malnutrition, une dysmorphie avec un front large et bomb\u00e9, une racine du nez large et un hypert\u00e9lorisme, des anomalies des cheveux qui sont fragiles, cassants, incoiffables et qualifi\u00e9s de \u00ab laineux \u00bb, un retard de croissance intra ut\u00e9rine et des anomalies de l\u2019immunit\u00e9 \u00e0 type de d\u00e9ficit en immunoglobuline ou d\u2019absence de r\u00e9ponse aux antig\u00e8nes vaccinaux. Des anomalies de deux prot\u00e9ines peuvent \u00eatre \u00e0 l\u2019origine du syndrome SD\/THE: <jats:italic>TTC37<\/jats:italic>, une prot\u00e9ine \u00e0 motif TPR et <jats:italic>SKIV2L<\/jats:italic>, une h\u00e9licase \u00e0 ARN, toutes 2 \u00e9tant des constituants du complexe SKI humain. Le complexe SKI est un co-facteur de l\u2019exosome cytoplasmique qui assure la d\u00e9gradation des ARN aberrants ou exog\u00e8nes. Le diagnostic est d\u2019abord clinique puis confirm\u00e9 par le s\u00e9quen\u00e7age des g\u00e8nes <jats:italic>TTC37<\/jats:italic> et <jats:italic>SKIV2L<\/jats:italic>. Le diagnostic diff\u00e9rentiel avec les autres formes de diarrh\u00e9es intraitables est fait gr\u00e2ce aux analyses anatomopathologiques qui montrent dans les autres formes, des l\u00e9sions sp\u00e9cifiques. La prise en charge clinique repose sur la nutrition parent\u00e9rale et la suppl\u00e9mentation en immunoglobuline si n\u00e9cessaire. Un certain nombre d\u2019enfants peuvent \u00eatre sevr\u00e9s de la nutrition parent\u00e9rale et des suppl\u00e9mentations en immunoglobulines. En cas d\u2019atteinte h\u00e9patique, celle-ci peut \u00eatre s\u00e9v\u00e8re et conduire au d\u00e9c\u00e8s. M\u00eame avec une prise en charge optimale, les enfants pr\u00e9sentent une petite taille et, dans la moiti\u00e9 des cas, un retard mental mod\u00e9r\u00e9.<\/jats:p>\n          <jats:p>Disease name\/synonyms \u2013 Syndromic diarrhea \u2013 Phenotypic diarrhea \u2013 Tricho-hepato-enteric syndrome \u2013 Intractable diarrhea of infancy with facial dysmorphism \u2013 Trichorrhexis nodosa and cirrhosis \u2013 Neonatal hemochromatosis phenotype with intractable diarrhea and hair abnormalities \u2013 Intractable infant diarrhea associated with phenotypic abnormalities and immune deficiency- Syndromatic diarrhea. [ORPHA84064 MIM 222470 and MIM614602]. Possibly chronic diarrhea and skin hyperpigmentation.<\/jats:p>","DOI":"10.1186\/1750-1172-8-5","type":"journal-article","created":{"date-parts":[[2013,1,10]],"date-time":"2013-01-10T00:01:05Z","timestamp":1357776065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Syndromic diarrhea\/Tricho-hepato-enteric syndrome"],"prefix":"10.1186","volume":"8","author":[{"given":"Alexandre","family":"Fabre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Martinez-Vinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Goulet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Badens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,1,9]]},"reference":[{"key":"500_CR1","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1002\/ajmg.a.31634","volume":"143","author":"A Fabre","year":"2007","unstructured":"Fabre A, Andr\u00e9 N, Breton A, Brou\u00e9 P, Badens C, Roquelaure B: Intractable diarrhea with \"phenotypic anomalies\" and tricho-hepato-enteric syndrome: two names for the same disorder. 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