Disease burden of Crigler-Najjar syndrome: Systematic review and future perspectives. J Gastroenterol Hepatol 2020 Apr;35(4):530-543
Date
09/10/2019Pubmed ID
31495946DOI
10.1111/jgh.14853Scopus ID
2-s2.0-85074581875 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
BACKGROUND AND AIM: Crigler-Najjar syndrome (CNS) results from biallelic mutations of UGT1A1 causing partial or total loss of uridine 5'-diphosphate glucuronyltransferase activity leading to unconjugated hyperbilirubinemia and its attendant risk for irreversible neurological injury (kernicterus). CNS is exceedingly rare and has been only partially characterized through relatively small studies, each comprising between two and 57 patients.
METHODS: A systematic literature review was conducted to consolidate data on the patient, caregiver, and societal burden of CNS.
RESULTS: Twenty-eight 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-I]), unconjugated bilirubin levels increase 3-6 mg/dL/day during the newborn period and reach neurologically dangerous levels between 5 and 14 days of age. Phototherapy is the mainstay of treatment but poses significant challenges to patients and their families. Despite consistent phototherapy, patients with CNS-I have worsening hyperbilirubinemia with advancing age. Liver transplantation is the only definitive therapy for CNS-I and is increasingly associated with excellent long-term survival but also incurs high costs, medical and surgical morbidities, and risks of immunosuppression.
CONCLUSIONS: Crigler-Najjar syndrome is associated with a substantial burden, even with existing standards of care. The development of novel disease-modifying therapies has the potential to reduce disease burden and improve the lives of CNS patients and their families.
Author List
Dhawan A, Lawlor MW, Mazariegos GV, McKiernan P, Squires JE, Strauss KA, Gupta D, James E, Prasad SAuthor
Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BilirubinCost of Illness
Crigler-Najjar Syndrome
Female
Gene Deletion
Glucuronosyltransferase
Humans
Hyperbilirubinemia
Infant, Newborn
Liver Transplantation
Male
Phototherapy
Rare Diseases
