ORIGINAL RESEARCH article
Front. Pediatr.
Sec. Pediatric Gastroenterology, Hepatology and Nutrition
Volume 13 - 2025 | doi: 10.3389/fped.2025.1582769
This article is part of the Research TopicPerspectives And Recent Advances In Rare Liver Diseases In ChildrenView all 4 articles
The role of LSR gene variants in early onset intrahepatic cholestasis: A case series with treatment options
Provisionally accepted
Sinja Ohlsson1*
Alex Zaufel2
Natalia Qvartskhava2
Friedrich Stock1Sophie Hinreiner3
Hideo Andreas Baba1
Benas Prusinskas4
Ralf Kubitz5Boris Görg2Diran Herebian2
Elke Lainka1
Simone Kathemann1- 1Essen University Hospital, Essen, Germany
- 2University Hospital of Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany
- 3Center of Human Genetics Regensburg, Regensburg, Bavaria, Germany
- 4Vilnius University Children's Hospital, Vilnius, Lithuania
- 5Bethanien Hospital, Moers, Germany
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We report on three children with novel variants in the lipolysis-stimulated lipoprotein receptor (LSR) gene with clinical presentation with early onset intrahepatic cholestasis and the main symptom being uncontrollable itching. Two patients showed dystrophy, short stature and microcephaly, whilst one patient had neurological developmental delay. LSR is one component of special tricellular tight junctions (tTJs) with expression in the liver and brain. We analyzed clinical data for all patients and performed multigene panel sequencing followed by Human Phenotype Ontology (HPO) based exome analysis, classifying the sequenced variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines. We performed immunostaining on the liver cryosections. The lack of LSR expression in immunofluorescence of the patients’ liver tissue confirmed the pathogenicity of genetic variants. We analyzed bile acids (BA) and their derivatives by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) in two of the three patients, confirming disturbed bile salt secretion. We also describe the use of an ileal bile acid transport (IBAT) inhibitor in two patients with LSR-associated intrahepatic cholestasis for the first time. Both patients showed a good response to the therapy in terms of itch control. In conclusion, LSR-associated early onset intrahepatic cholestasis is a new and likely underdiagnosed disease. Patients with an unclear progressive familial intrahepatic cholestasis (PFIC)-like clinical picture should therefore undergo genetic testing of the LSR gene. Treatment with an IBAT inhibitor should be considered.
Keywords: infantile intrahepatic cholestasis, early onset intrahepatic cholestasis, LSR gene, Pruritus, Itching, microcephaly Progressive familiar intrahepatic cholestasis, IBAT inhibitor
Received: 24 Feb 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Ohlsson, Zaufel, Qvartskhava, Stock, Hinreiner, Baba, Prusinskas, Kubitz, Görg, Herebian, Lainka and Kathemann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sinja Ohlsson, Essen University Hospital, Essen, Germany
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