Abstract: Objective To investigate the clinical characteristics and prognosis of regression in children with congenital non-hemolytic unconjugated hyperbilirubinemia starting in the neonatal period in Zhangjiajie, Hunan Province. Methods Clinical data of 19 full-term congenital non-hemolytic unconjugated hyperbilirubinemiac children admitted to the neonatal unit of Zhangjiajie People's Hospital were collected during their hospitalization, and their clinical manifestations, peripheral blood test characteristics, genetic diagnosis, prognosis of primary disease and follow-up results were summarized and analyzed.Results Nineteen children with congenital nonhemolytic unconjugated hyperbilirubinemia were finally diagnosed by whole-exome sequencing, and six mutation loci encoding bilirubin-uridine diphosphate glucuronosyltransferase (UGT1A1) were identified, and all mutation types were missense mutations, including 10 pure mutations alone (52.6%), 5 pure heterozygous mutations (26.3%) and 4 compound heterozygous mutations (21.1%), with 2 and 17 cases in Han and Tu families, respectively. The most common clinical manifestation was severe skin jaundice, and 14 children had severe or higher hyperbilirubinemia (>342 μmol/L) 7 children received simultaneous peripheral arteriovenous blood exchange and intermittent double-sided blue light therapy, and the median time of receiving blood exchange therapy was 7.2 d postnatally (Interquartile spacing： 5.9, 7.3 d), and the average time of receiving light therapy was (34.7±17.0) h. 12 children received intermittent double-sided blue light therapy. After treatment, the serum indirect bilirubin level decreased compared to the previous level. At follow-up, the basic growth and development of all 19 children were found to be fair, with one case of typical bilirubin encephalopathy in the short term, with gradual improvement of symptoms after 2 months of age.Conclusion In our group, the majority of congenital non-hemolytic unconjugated hyperbilirubinemia cases had serum bilirubin values exceeding the level of severe hyperbilirubinemia, and the pathogenesis was mainly associated with c.211G>A, c.1091C>T, c.1318A>G, c.1348C>T, c.686C>A, and c.1456T>G mutations, with c.211G>A simple pure mutations the most common; the primary symptoms of congenital non-hemolytic unconjugated hyperbilirubinemia were relieved by simultaneous peripheral arteriovenous blood exchange and two-sided blue light therapy. Simultaneous peripheral arteriovenous blood exchange and intermittent two-sided blue light therapy can alleviate the primary symptoms in children with congenital non-hemolytic unconjugated hyperbilirubinemia, but it is still necessary to be alert for complications such as neonatal bilirubin encephalopathy and cholestatic hepatitis during treatment and follow-up.

Key words: Neonates, UGT1A1 gene, Congenital, Severe hyperbilirubinemia