Molecular analysis of patients of Sardinian descent with Crigler-Najjar syndrome type I.

This study reports the molecular characterisation of the bilirubin UDP-glucuronosyl-transferase gene (UGT1) in a group of patients of Sardinian descent with Crigler-Najjar syndrome type I and their relatives. Sequence analysis of both UGT1A exon 1 and common exons 2-5 was performed in all patients, leading to the detection of AF170 and a novel mutation (470insT), both residing in UGT1A exon 1. All but two heterozygotes for the AF170 mutation showed normal serum bilirubin levels. These two subjects were also heterozygous for the sequence variation A(TA)7TAA in the promoter region of the UGT1A gene.

Biliary, anorectal and esophageal atresia: a new entity?

A unique case of newborn biliary atresia associated with esophageal atresia and tracheoesophageal fistula, ano-rectal atresia, Reovirus type 3 infection and an early switch of fetal into adult hemoglobin is reported. At birth, the infant, who had only one umbilical artery, was operated on by primary anastomosis of the esophagous, and descending colostomy. At six weeks of age the baby underwent a "Kasai hepatic portoenterostomy-Type I" for a EHBA Type III, Subtype C2, Subgroup O ("aplasia" of all extrahepatic biliary ducts, including the gallbladder). The absence of an artery branch for the left lobe of the liver was observed. Histologically, the liver showed a hyperplasia of the intrahepatic bile ducts due to persistence of an excess of embryologic bile ducts in "ductal plate malformation" (DPM). Specific Reovirus type 3 antibodies were found in both the mother's and baby's sera. In the postoperative period the infant developed rapid and severe liver failure and underwent a successful liver transplantation. Although in most cases EHBA appears to be a perinatal event due to a necro-inflammatory process of unknown etiology, cases associated with complex extrahepatic anomalies, may be due to different pathogenetic mechanisms supported by different causative agents operating very early in the fetal period. Viral infection seems to be the most reliable etiology.