Abstract

Citrin deficiency (CD) is an autosomal recessive disorder and represents one of the urea cycle disorders. This study aims to analyze the detection rate, clinical features, and genetic mutation characteristics of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in the Hefei region of China. We conducted NICCD screening using tandem mass spectrometry (MS/MS) for infants born in Hefei City between January 2016 and December 2025. Screen-positive cases were subjected to genetic testing via next-generation sequencing (NGS), with subsequent validation by Sanger sequencing. Clinical manifestations, biochemical parameters, and genetic mutation profiles of confirmed cases were systematically analyzed. A total of 924,676 newborns underwent screening, identifying 17 cases of NICCD, yielding a detection rate of 1/54,393, with two false-negative cases identified. The most prevalent mutation site is c.852_855del (p.M285Pfs*2). Following diagnosis, health education, dietary guidance, and symptomatic treatment were administered, resulting in favorable outcomes in the majority of cases. However, one infant exhibited significant growth retardation despite early therapeutic intervention that normalized biochemical parameters. Furthermore, an infant was found to have gallstones at birth and subsequently diagnosed with a liver hemangioma at one year of age. Some patients may experience missed screenings due to delayed elevations in citrulline levels. Therefore, even for newborns with negative screening results, timely assessments of liver function, MS/MS, and genetic testing are recommended for infants experiencing prolonged jaundice. This approach enables early identification and intervention. The combination of MS/MS with genetic screening may serve as a reliable strategy to reduce false-negative results in NICCD screening.

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