{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:15Z","timestamp":1784557035948,"version":"3.55.0"},"reference-count":10,"publisher":"Bioscientifica","content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,9,20]]},"abstract":"Summary<\/jats:title>\n \n Wolcott\u2013Rallison syndrome (WRS) is a rare autosomal recessive disorder due to mutations in the\n EIF2AK3<\/jats:italic>\n gene. It is characterized by permanent neonatal diabetes mellitus, skeletal dysplasia, liver impairment, neutropenia and renal dysfunction. Liver is the most commonly affected organ and liver failure is the commonest cause of death in this syndrome. The\n EIF2AK3<\/jats:italic>\n gene encodes a transmembrane protein PERK, which is important for the cellular response to endoplasmic reticulum (ER) stress. The absence of PERK activity reduces the ER\u2019s abilities to deal with stress, leading to cell death by apoptosis. On acquiring febrile illness, affected patients suffer from liver injury, which may progress into liver failure and death. Renal involvement is less common and is mainly in the form of functional renal impairment at the advanced stage of the disease. Structural renal anomalies have not been reported in WRS. We report a 6-month-old girl who presented with neonatal diabetes on day 1 of life. Her genetic testing confirmed WRS due to missense mutation in the\n EIF2AK3<\/jats:italic>\n gene (c.2867G\u2009>\u2009A, p.Gly956Glu). Parents are first-degree cousins and both are heterozygous carriers to the mutation. 2 paternal uncles had the same mutation and died of liver disease at 1 and 14 years of age. Neither had a renal disease. She presented with hematuria during a febrile illness at the age of 5 months. Ultrasound scan showed right ectopic multicystic dysplastic kidney (MCDK). To the best of our knowledge, this is the first patient with WRS who is reported to have an MCDK disease.\n <\/jats:p>\n \n Learning points:<\/jats:title>\n \n \n Neonatal diabetes should be considered in babies presenting with early hyperglycemia particularly if there is a family history.<\/jats:p>\n <\/jats:list-item>\n \n Genetic diagnosis in neonatal diabetes enables disease confirmation, genetic counseling and anticipation of potential complications during concomitant situations such as acute illness, trauma or major surgery.<\/jats:p>\n <\/jats:list-item>\n \n There is lack of phenotype\u2013genotype correlation in Wolcott\u2013Rallison syndrome.<\/jats:p>\n <\/jats:list-item>\n \n Structural kidney abnormality, in our case MCDK, can be seen in WRS.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-17-0090","type":"journal-article","created":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T04:44:32Z","timestamp":1505882672000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":2,"title":["Multicystic dysplastic kidney: a new association of Wolcott\u2013Rallison syndrome"],"prefix":"10.1530","volume":"2017","author":[{"given":"Asma","family":"Deeb","sequence":"first","affiliation":[{"name":"1Paediatric Endocrinology Department, Mafraq Hospital, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Al-Zidgali","sequence":"additional","affiliation":[{"name":"2Neonatology Department, Corniche Hospital, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibian N","family":"Ofoegbu","sequence":"additional","affiliation":[{"name":"2Neonatology Department, Corniche Hospital, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"key20170929130119065_bib1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/78085","article-title":"EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome","volume":"25","author":"Del\u00e9pine","year":"2000","journal-title":"Nature Genetics"},{"key":"key20170929130119065_bib2","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1128\/MCB.22.11.3864-3874.2002","article-title":"The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas","volume":"22","author":"Zhang","year":"2002","journal-title":"Molecular and Cellular Biology"},{"key":"key20170929130119065_bib3","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1159\/000369804","article-title":"Liver disease and other comorbidities in Wolcott-Rallison syndrome: different phenotype and variable associations in a large cohort","volume":"83","author":"Habeb","year":"2015","journal-title":"Hormone Research in Paediatrics"},{"key":"key20170929130119065_bib4","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1007\/s00467-005-1881-1","article-title":"Familial multicystic dysplastic kidney.","volume":"20","author":"Watanabe","year":"2005","journal-title":"Pediatric Nephrology"},{"key":"key20170929130119065_bib5","first-page":"263","article-title":"Familial hypoplastic glomerulocystic kidney: a new entity?","volume":"18","author":"Rizzoni","year":"1982","journal-title":"Clinical Nephrology"},{"key":"key20170929130119065_bib6","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1086\/503875","article-title":"Quantification of homozygosity in consanguineous individuals with autosomal recessive disease","volume":"78","author":"Woods","year":"2006","journal-title":"American Journal of Human Genetics"},{"key":"key20170929130119065_bib7","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/pedi.12201","article-title":"Microscopic and ultrastructural features in Wolcott-Rallison syndrome, a permanent neonatal diabetes mellitus: about two autopsy cases","volume":"16","author":"Collardeau-Frachon","year":"2015","journal-title":"Pediatric Diabetes"},{"key":"key20170929130119065_bib8","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/jmg.40.9.685","article-title":"Wolcott-Rallison syndrome: pathogenic insights into neonatal diabetes from new mutation and expression studies of EIF2AK3","volume":"40","author":"Brickwood","year":"2003","journal-title":"Journal of Medical Genetics"},{"key":"key20170929130119065_bib9","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/ajmg.a.37419","article-title":"Genetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of Abu Dhabi, United Arab Emirates","volume":"170","author":"Deeb","year":"2015","journal-title":"American Journal of Medical Genetics Part A"},{"key":"key20170929130119065_bib10","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1210\/jc.2009-1137","article-title":"Wolcott\u2013Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families","volume":"94","author":"Rubio-Cabezas","year":"2009","journal-title":"Journal of Clinical Endocrinology and Metabolism"}],"container-title":["Endocrinology, Diabetes & Metabolism Case Reports"],"original-title":[],"link":[{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2017\/1\/EDM17-0090.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2017\/1\/EDM17-0090.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:46:39Z","timestamp":1784555199000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/edm\/article\/3434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,20]]},"references-count":10,"URL":"https:\/\/doi.org\/10.1530\/edm-17-0090","relation":{},"ISSN":["2052-0573"],"issn-type":[{"value":"2052-0573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,20]]}}}