{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:16:32Z","timestamp":1789654592607,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T00:00:00Z","timestamp":1553212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010147","name":"Asociaci\u00f3n Espa\u00f1ola de Pediatr\u00eda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>ARC (arthrogryposis, renal dysfunction, and cholestasis) syndrome is an uncommon multisystem disorder that entails a very poor prognosis. It is caused by mutations in either <jats:italic>VPS33B<\/jats:italic> or <jats:italic>VIPAS39<\/jats:italic> gene, both playing a key role in intracellular trafficking. We report two siblings born to first cousin parents with a novel mutation in <jats:italic>VPS33B<\/jats:italic> who have both shown prolonged survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Cases Presentation<\/jats:title><jats:p>The index patient presented with bilateral hip dysplasia and arthrogryposis, failure to thrive, undernourishment, developmental delay, and low gamma\u2010glutamyl transferase cholestasis. She at age 2\u2009years underwent external biliary diversion with improvement in pruritus but liver disease continued to progress. She developed stomal bleeding at 7\u2009years of age and liver biopsy displayed cirrhosis. Her 3\u2010year\u2010old sibling showed a similar trajectory as well as he had ichthyotic skin with excoriations. Their renal involvement was mild and stable. Genetic analysis in both patients revealed a novel homozygous mutation in NM_018668.4 (<jats:italic>VPS33B<\/jats:italic>):c.1157A\u2009&gt;\u2009C (p.His386Pro).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ARC syndrome is a severe disorder with few patients reported to survive beyond 12\u2009months of age. This report discloses a novel mutation in the <jats:italic>VPS33B<\/jats:italic> gene and describes a phenotype with prolonged survival, mild renal involvement, and progressive liver disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmd2.12027","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T14:52:17Z","timestamp":1557499937000},"page":"4-8","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A novel mutation in <i>VPS33B<\/i> gene causing a milder ARC syndrome phenotype with prolonged survival"],"prefix":"10.1002","volume":"47","author":[{"given":"Rodrigo","family":"del Br\u00edo Castillo","sequence":"first","affiliation":[{"name":"Pediatric Liver Service Hospital Infantil Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Squires","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"McKiernan","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,22]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1","article-title":"Familiare gallengangs missbildungen mit tubularer neireninsurfizienz","volume":"28","author":"Lutz\u2010Richner A","year":"1973","journal-title":"Helv Paediatr 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