249 Unusual incidence of crigler-najjar syndrome type 1 in Croatia

• Published in: Archives of disease in childhood 2021-10, Vol.106 (Suppl 2), p.A105-A105
• Main Authors: Todorić, Ivana, Aničić, Mirna Natalija, Omerza, Lana, Senečić-Čala, Irena, Tješić-Drinković, Duška, Vuković, Jurica
• Format: Article
• Language: English
• Subjects: Abstracts; Bilirubin; Crigler-Najjar syndrome; Epigenetics; Females; Frameshift mutation; Genetic screening; Hereditary diseases; Hyperbilirubinemia; Liver; Liver transplantation; Liver transplants; Mutation; Nonsense mutation; Offspring; Patients; Pediatrics; Phototherapy; Siblings; Uridine
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/archdischild-2021-europaediatrics.249

To present patients with Crigler-Najjar syndrome type 1 (CN1). It is a rare autosomal recessive disorder with an incidence of 1: 1 000 000 live births, characterised by severe unconjugated hyperbilirubinemia which arises as a consequence of the absence of hepatic bilirubin uridine diphosphate glucuronosyl transferase(UGT1A1) activity.In the last 30 years we treated seven children with this syndrome at the Department of Pediatrics, University Hospital Center Zagreb.They were from five families- two pairs of siblings (brother and sister) and three unrelated patients (two boys and a girl). Genetic testing of UGT1A1 gene was performed in six patients (two pairs of siblings and two unrelated boys). Unfortunately, one patient’s result was lost.Three patients had frameshift mutations in exon 1: Patient 1 (c.722_723delAG p.Glu241Glyfs*16), Patients 2 and 3 were siblings and had identical mutation (c.717_718delAG p.Q239fsX256). Two patients (4 and 5, also siblings) had identical nonsense mutation in exon 3 (c.1021C>T p.Arg341*).Genetic testing, as it was not widely available at the time, was not performed in one girl whose diagnosis was made by the chromatographic analysis of bilirubin glucuronides in the bile.Four patients underwent a liver transplant from living related donors. In two auxillary procedure was performed (siblings at the age of 7 and 9 years) and in two segmental liver transplant (at the age of 6 and 10 years). Prior to surgery, there was also an unsuccessful attempt of hepatocyte transplantation in one patient.Three liver transplant procedures were successful, and one patient died in the early post-operative course due to primary graft dysfunction.Three patients who have not yet undergone liver transplant (a 3-year-old boy and two siblings 1.5-year-old girl and her 6-month-old brother) are currently treated with phototherapy. At least 10-14 hours long treatment is necessary to keep their bilirubin at an acceptable level (around 250 umol/L). Their psychomotor development is appropriate and they have no neurologic impairment.Considering the number of births per year in Croatia we noticed a remarkably high incidence of CN1, more than five times as expected (5,4: 1 000 000). We don’t have explanation for this finding, at least not by mutations observed. Nevertheless, three of our patients are offspring of two families originating in small Croatian enclave in Kosovo where they were isolated for several centuries. Perhaps there are epigenetic factors we