Disease burden of Crigler-Najjar syndrome: systematic review and future perspectives.J Gastroenterol Hepatol 2019JG
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.
We conducted a systematic literature review to consolidate data on the patient, caregiver, and societal burden of CNS.
We identified 28 articles on clinical aspects of CNS, but found no published data on its humanistic or economic burden. In patients with complete UGT1A1 deficiency (type 1 CNS [CNS-I]), unconjugated bilirubin levels increase 3-6 mg/dL per 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.
CNS 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.