P53 Mutation at Codon 249 is Uncommon in Neonatal Kotb Disease Biliary Atresia

: Background: Hepatocellular carcinoma (HCC) is known to result from aflatoxin B1 that induces p53 mutation at codon 249. Aflatoxins are also known to cause The Kotb disease Biliary atresia (BA) variant which is characterized by congenital aflatoxicosis B1 in neonates with null glutathione S transferase M1. Aim of the Work: We aimed to search for the aflatoxin B1 induced HCC 249 codon p53 mutation among neonates with Kotb disease BA variant and their mothers. Patients and Methods: This study included 13 neonates and infants with confirmed BA who presented to Hepatology Clinic, New Children Hospital, Cairo University, Egypt during January-May 2019. All subjects and their mothers underwent detection of aflatoxins from peripheral blood. BA cases underwent detection of mutation from liver biopsy tissue as well. Results: The studied cohort with confirmed BA comprised 9 (69.2%) girls and 4 (30.8%) boys, with mean ages ± standard deviation (SD) at onset, presentation, diagnosis and portoenterostomy of 8.1±5.7 days, 44.8±11 days, 57±14.53 and 64.5±21.34 days respectively. All 13 and their mothers were found to have elevated blood levels of aflatoxin B1 with a mean of 8.56 ± 4.2ng/ml and 14.75±16.78ng/ml respectively. The mean ± SD duration of follow up was 259.1±141 days. None of the mothers had abnormal levels of bilirubin or liver aminotransferases. All samples tested negative for p53 mutation at codon 249 except for one infant who tested negative for the mutation in his whole blood and had heterozygous mutation in DNA from his liver tissue. None of the studied cohort or their mothers had HCC. Cholestasis resolved in 2 children, 7 had progressive course and 4 died. There was no correlation between outcome and neonate/maternal aflatoxin B1 level (p=0.299; p=0.443), age at portoenterostomy (p=0.93), hepatic fibrosis degree (p=0.56), or other lab or liver biopsy findings. Conclusion: p53 mutation at codon 249 is uncommon in infants with Kotb disease BA variant, despite the aflatoxicosis they suffer from. The cause remains to be studied. Screening for p53 mutation at codon 249 cannot be used as a diagnostic test for Kotb disease.