Bile Duct Paucity in Infancy

Approach to an infant with jaundice and persistent conjugated hyperbilirubinemia includes several pediatric investigations with a different spectrum of invasiveness ranging from clinical biochemistry to liver biopsy. The broad and intense level of investigation needs to be set up soon to exclude surgical conditions that would prompt the child to a beneficial at least temporary solution. Paucity of the interlobular bile ducts (PIBD) is defined as a low ratio of interlobular bile ducts to portal tract ratios. However, obtaining adequate tissue for a definitive diagnosis can be a problem in young children. The interlobular bile duct to portal tract ratio is a value that has been considered differently from several authors, but major consensus and discussion platforms among pathologists and hepatologists seem indicate a cut-off value of 0.6 as highly likely for PIBD. PIBD may occur in a non-syndromic setting with various conditions or in genetic syndromes with a peculiar association with simple or complex congenital heart disease. Two wellestablished syndromes have been identified as genetic syndromes with a PIBD, although the list of the syndromes may be growing in the future. The first syndrome described in the literature is Alagille syndrome (AGS) or arteriohepatic dysplasia with pulmonary stenosis as the most common cardiac single finding and tetralogy of Fallot as the most common complex cardiac defect. Alagille syndrome can be caused by either mutation in the Jagged-1 gene (JAG1) mutation or in the NOTCH2 gene (Bauer et al. 2010). The second syndrome is Williams-Beuren syndrome (WBS), which is a neurodevelopmental disorder with supravalvular aortic or pulmonary stenosis. The WBS is associated with a microdeletion within the 7q11.23 chromosomal band, which encompasses 28 genes and specific low copy repeats serve as substrate for non-allelic homologous recombination leading to the deletion. The most common deletion, which occurs in about 95% of cases, involves a 1.5 megabase DNA segment (Henrichsen et al. 2011). Interestingly, in both genetic syndromes an abnormality of the outlet tract of the ventricular pump of the heart represents one of the most salient feature.