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Case Reports
. 2025 Nov;55(11):1551-1556.
doi: 10.1111/hepr.70003. Epub 2025 Jul 18.

Lipolysis-Stimulated Lipoprotein Receptor Gene Variants as a Cause of Progressive Familial Intrahepatic Cholestasis: A Case Report

Yugo Takaki  1 , Shuichiro Umetsu  2 , Yoshihiko Sugino  3 , Takahiro Yamashita  3 , Takehiko Doi  4 , Kazuo Imagawa  5 , Shogo Ito  6 , Yutaro Mihara  7 , Hisamitsu Hayashi  8 , Ayano Inui  2
Affiliations
Case Reports

Lipolysis-Stimulated Lipoprotein Receptor Gene Variants as a Cause of Progressive Familial Intrahepatic Cholestasis: A Case Report

Yugo Takaki et al. Hepatol Res. 2025 Nov.

Abstract

Aim: To investigate the genetic and molecular mechanisms underlying intrahepatic cholestasis associated with lipolysis-stimulated lipoprotein receptor (LSR) deficiency and to evaluate its potential role in conditions similar to progressive familial intrahepatic cholestasis (PFIC).

Case presentation: We studied a 4-year-old girl with no significant perinatal history who presented with symptoms of cholestasis-pruritus, poor weight gain, and darkened skin-by 6 months of age. Laboratory tests revealed mild cholestasis with elevated total bile acids and normal gamma-glutamyl transferase (GGT). A liver biopsy revealed chronic cholestasis and mild fibrosis. Whole-exome sequencing identified two compound heterozygous variants in the LSR gene, and immunostaining confirmed reduced LSR expression in the liver. The patient showed persistent cholestasis, normal GGT, and a clinical presentation suggestive of PFIC. Genetic testing revealed LSR gene variants, including a likely pathogenic duplication, confirming LSR deficiency. Despite treatment with ursodeoxycholic acid (UDCA), her pruritus persisted and growth remained stunted. Developmental delays were primarily noted in language acquisition.

Conclusions: This case suggests that LSR deficiency may contribute to a PFIC-like condition, thus broadening our understanding of the genetic causes of intrahepatic cholestasis. Children presenting with PFIC-like symptoms but without mutations in known PFIC genes should be evaluated for LSR deficiency. Further research is needed to elucidate LSR's role in liver function and its potential classification as a new PFIC subtype, "PFIC-14."

Keywords: progressive familial intrahepatic cholestasis; the lipolysis‐stimulated lipoprotein receptor; tricellular tight‐junction proteins.

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References

    1. S. Masuda, Y. Oda, H. Sasaki, et al., “LSR Defines Cell Corners for Tricellular Tight Junction Formation in Epithelial Cells,” Journal of Cell Science 124, no. 4 (2011): 548–555: PMID 21245199, https://doi.org/10.1242/jcs.072058.
    1. S. Maddirevula, H. Alhebbi, A. Alqahtani, et al., “Identification of Novel Loci for Pediatric Cholestatic Liver Disease Defined by KIF12, PPM1F, USP53, LSR, and WDR83OS Pathogenic Variants,” Genetics in Medicine 21, no. 5 (2019): 1164–1172: PMID 30250217, https://doi.org/10.1038/s41436‐018‐0288‐x.
    1. T. Uehara, M. Yamada, S. Umetsu, et al., “Biallelic Mutations in the LSR Gene Cause a Novel Type of Infantile Intrahepatic Cholestasis,” Journal of Pediatrics 221 (2020): 251–254: PMID 32303357, https://doi.org/10.1016/j.jpeds.2020.01.064.
    1. L. N. Bull, M. J. van Eijk, L. Pawlikowska, et al., “A Gene Encoding a P‐type Atpase Mutated in Two Forms of Hereditary Cholestasis,” Nature Genetics 18, no. 3 (1998): 219–224: PMID 9500542, https://doi.org/10.1038/ng0398‐219.
    1. S. S. Strautnieks, L. N. Bull, A. S. Knisely, et al., “A Gene Encoding a Liver‐specific ABC Transporter Is Mutated in Progressive Familial Intrahepatic Cholestasis,” Nature Genetics 20, no. 3 (1998): 233–238: PMID 9806540, https://doi.org/10.1038/3034.

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