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CNS is exceedingly rare and has been only partially characterized through relatively small studies, each comprising between two and 57 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic literature review was conducted to consolidate data on the patient, caregiver, and societal burden of CNS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010eight articles on clinical aspects of CNS were identified, but no published data on its humanistic or economic burden were found. In patients with complete UGT1A1 deficiency (type 1 CNS [CNS\u2010I]), unconjugated bilirubin levels increase 3\u20136\u00a0mg\/dL\/day during the newborn period and reach neurologically dangerous levels between 5 and 14\u00a0days of age. Phototherapy is the mainstay of treatment but poses significant challenges to patients and their families. Despite consistent phototherapy, patients with CNS\u2010I have worsening hyperbilirubinemia with advancing age. Liver transplantation is the only definitive therapy for CNS\u2010I and is increasingly associated with excellent long\u2010term survival but also incurs high costs, medical and surgical morbidities, and risks of immunosuppression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Crigler\u2013Najjar syndrome is associated with a substantial burden, even with existing standards of care. The development of novel disease\u2010modifying therapies has the potential to reduce disease burden and improve the lives of CNS patients and their families.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.14853","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T06:10:48Z","timestamp":1568009448000},"page":"530-543","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Disease burden of Crigler\u2013Najjar syndrome: Systematic review and future perspectives"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4942-0845","authenticated-orcid":false,"given":"Anil","family":"Dhawan","sequence":"first","affiliation":[{"name":"King's College Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine and Neuroscience Research Center Medical College of Wisconsin  Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George V","family":"Mazariegos","sequence":"additional","affiliation":[{"name":"Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh University of Pittsburgh School of Medicine  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"McKiernan","sequence":"additional","affiliation":[{"name":"Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh University of Pittsburgh School of Medicine  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6979-8987","authenticated-orcid":false,"given":"James E","family":"Squires","sequence":"additional","affiliation":[{"name":"Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh University of Pittsburgh School of Medicine  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A","family":"Strauss","sequence":"additional","affiliation":[{"name":"Clinic for Special Children  Strasburg PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Digant","family":"Gupta","sequence":"additional","affiliation":[{"name":"Bridge Medical Consulting Ltd  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"James","sequence":"additional","affiliation":[{"name":"Audentes Therapeutics  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyash","family":"Prasad","sequence":"additional","affiliation":[{"name":"Audentes Therapeutics  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,24]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"169","article-title":"Congenital familiar nonhemlytic jaundice with kernicterus","volume":"10","author":"Crigler JF","year":"1952","journal-title":"Pediatr"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00014330"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/17446651.3.6.725"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00359-8"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678707.2018.1495558"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i38.6398"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.247"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198502000-00010"},{"key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1542\/peds.69.3.267","article-title":"A clinical pathologic reappraisal of kernicterus","volume":"69","author":"Turkel SB","year":"1982","journal-title":"Pediatrics"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510240205"},{"key":"e_1_2_6_12_1","first-page":"486","article-title":"Management of Crigler\u2013Najjar syndrome type I","volume":"22","author":"Al\u2010Shurafa HA","year":"2001","journal-title":"Saudi. 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