Analysis of cholestasis infants with low to normal gamma-glutamyl transferase level
Keywords:
Neonatal cholestatic jaundice, Low to normal gamma-glutamyl transferase (GGT) levelAbstract
Background: Neonatal cholestatic jaundice with low to normal gamma-glutamyl transferase (GGT) is infrequent but clinically significant and associated with a wide spectrum of genetic diseases, including progressive familial intrahepatic cholestasis (PFIC). Among these, mutations in the ABCB11 gene are a prominent etiology, as encodes the bile salt export pump (BSEP) are a prominent etiology.
Objective: To investigate the ABCB11 mutations in neonatal cholestatic jaundice with low to normal GGT levels.
Methods: A prospective study was conducted from 2017 to 2021 at Srinagarind Hospital, Khon Kaen, Thailand. Six neonates with cholestasis and low to normal GGT were enrolled. After exclusion of infectious, surgical, and syndromic causes. Urine bile acid analysis was performed to exclude bile acid synthesis defects. DNA was extracted and sequenced in all 28 exons of the ABCB11 gene using next-generation sequencing.
Results: All 6 patients revealed biochemical evidence of cholestasis and liver histological features of hepatocellular injury. No pathogenic mutations were identified in the ABCB11 gene; only benign variants and variants of uncertain significance (VUS) were detected.
Conclusion: The undetectable of pathogenic ABCB11 mutations highlights the need for expanded genomic analysis and functional testing.
Downloads
References
Kim SR, Saito Y, Itoda M, Maekawa K, Kawamoto M, Kamatani N, et al. Genetic variations of the ABC transporter gene ABCB11 encoding the human bile salt export pump (BSEP) in a Japanese population. Drug Metab Pharmacokinet. 2009;24:277–81.
Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol. 2014;4:25–36.
Kalaranjini KV, Glaxon JA, Vasudevan S, Arunkumar ML. Benign recurrent intrahepatic cholestasis - 2 (BRIC-2)/ABCB11 deficiency in a young child - Report from a tertiary care center in South India. Indian J Pathol Microbiol. 2021;64:S146–8.
Strautnieks SS, Byrne JA, Pawlikowska L, Cebecauerová D, Rayner A, Dutton L, et al. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology. 2008;134:1203–14.
Lockitch G, Halstead AC, Albersheim S, MacCallum C, Quigley G. Age- and sex-specific pediatric reference intervals for biochemistry analytes as measured with the Ektachem-700 analyzer. Clin Chem. 1988;34:1622-5.
Riaz H, Zheng B, Zheng Y, Liu Z, Gu HM, Imran M, et al. The spectrum of novel ABCB11 gene variations in children with progressive familial intrahepatic cholestasis type 2 in Pakistani cohorts. Sci Rep. 2024;14:18876.
Kondou H, Nakano S, Mizuno T, Bessho K, Hasegawa Y, Nakazawa A, et al. Clinical symptoms, biochemistry, and liver histology during the native liver period of progressive familial intrahepatic cholestasis type 2. Orphanet J Rare Dis. 2024;19:57.
Davit-Spraul A, Fabre M, Branchereau S, Baussan C, Gonzales E, Stieger B, et al. ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): Phenotypic differences between PFIC1 and PFIC2 and natural history. Hepatology. 2010;51:1645–55.
Selim N, Omair H, El-Karaksy H, Fathy M, Mahmoud E, Baroudy S, et al. A study of exons 14, 15, and 24 of the Abcb11 gene in Egyptian children with normal GGT cholestasis. Arab J Gastroenterol. 2022;23:15–9.
Mínguez Rodríguez B, Molera Busoms C, Martorell Sampol L, García Romero R, Colomé Rivero G, Martín de Carpi J. Heterozygous mutations of ATP8B1, ABCB11 and ABCB4 cause mild forms of progressive familial intrahepatic cholestasis in a pediatric cohort. Gastroenterol Hepatol. 2022;45:585–92.
Treepongkaruna S, Gaensan A, Pienvichit P, Luksan O, Knisely AS, Sornmayura P, et al. Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic cholestasis. World J Gastroenterol. 2009;15:4339-42.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 The Royal College of Pediatricians Of Thailand
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
