Oral

Introduction and Objectives :
With the advances in molecular genetics, neonatal cholestasis gene panel is frequently being used to test various candidate genes for neonatal cholestasis. The aim of this study is to evaluate clinical application of single-gene testing and next-generation sequencing(NGS) and to develop diagnostic algorithm for neonatal intrahepatic cholestasis.

Methods :
From January 2010 to July 2021, 148 patients suspected with intrahepatic neonatal cholestasis at Seoul National University Hospital were tested. If there was a clinically suspected disease, single-gene testing was performed, and if clinically difficult to differentiate, neonatal cholestasis gene panel containing 34 genes was performed. Then we compared clinical data of genetically confirmed neonatal cholestasis patients.

Results :
Of the total 148 patients, 49(33.1%) were confirmed by genetic analysis, including 14 with Alagille syndrome(ALGS), 14 with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), 7 with Dubin-Johnson syndrome, 5 with Arthrogryposis-renal dysfunction-cholestasis syndrome, 5 with bile salt export pump deficiency, 1 with Rotor syndrome, 1 with Niemann-Pick disease type C, 1 with Kabuki syndrome, and 1 with FARSA mutation. A total of 16 novel pathogenic or likely pathogenic variants for neonatal cholestasis were observed in this study. Based on clinical characteristics and laboratory findings, we developed the diagnostic algorithm for intrahepatic neonatal cholestasis integrating single-gene testing and NGS.

Conclusions :
ALGS and NICCD are most common disease in genetic neonatal cholestasis. Single-gene testing and NGS are important and complementary to the diagnosis of genetic neonatal cholestasis.

Key words :
neonatal jaundice, intrahepatic cholestasis, next-generation sequencing