GGT-normal cholestasis associated with LSR deficiency: A potential new subtype of PFIC

Abstract

Introduction: Hereditary cholestatic liver diseases are a group of disorders caused by different gene mutations encoding proteins involved in bile production, transport, or secretion. New genetic disorders have been identified in cholestatic patients through an increased understanding of these proteins, evolving genetic technology and more widespread genetic testing. Recently, mutations in the Lipolysis-Stimulated Lipoprotein Receptor (LSR) gene have been identified as a novel cause of infantile intrahepatic cholestasis. To date, only two cases have been reported in the literature. Here, we present two children with GGT normal cholestasis with LSR-gene variants.

Methods: Two pediatric patients with GGT-normal cholestasis underwent genetic analysis, including whole-exome sequencing. Clinical, laboratory, and histopathological findings were reviewed, and genetic variants were evaluated.

Results: Both patients exhibited progressive cholestasis with normal GGT levels, and genetic analysis identified homozygous missense variants in the LSR gene. These cases' clinical presentation and disease course shared similarities with previously reported LSR-related cholestasis, suggesting a common pathogenic mechanism.

Conclusions: These findings further support the LSR gene as a novel cause of GGT normal cholestasis. Identifying additional cases provides crucial insights into the genotype-phenotype correlation, aiding in the early diagnosis and management of affected patients. Expanding the number of reported cases will contribute to a better understanding of disease progression and potential therapeutic strategies.

Keywords: Bile transport disorder; Cholestasis; GGT-normal cholestasis; Genetic liver disease; Intrahepatic cholestasis; LSR gene; Pediatric hepatology.