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World J Hepatol. Oct 27, 2022; 14(10): 1844-1861
Published online Oct 27, 2022. doi: 10.4254/wjh.v14.i10.1844
Natural history and management of liver dysfunction in lysosomal storage disorders
Moinak Sen Sarma, Parijat Ram Tripathi
Moinak Sen Sarma, Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
Parijat Ram Tripathi, Department of Pediatric Gastroenterology, Ankura Hospital for Women and Children, Hyderabad 500072, India
Author contributions: Sen Sarma M contributed to the conception and final drafting of the manuscript; Tripathi PR contributed to the data collation and primary drafting of the manuscript.
Conflict-of-interest statement: No conflict of interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Moinak Sen Sarma, MD, Associate Professor, Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India.
Received: December 27, 2021
Peer-review started: December 27, 2021
First decision: March 7, 2022
Revised: April 21, 2022
Accepted: September 21, 2022
Article in press: September 21, 2022
Published online: October 27, 2022

Lysosomal storage disorders (LSD) are a rare group of genetic disorders. The major LSDs that cause liver dysfunction are disorders of sphingolipid lipid storage [Gaucher disease (GD) and Niemann-Pick disease] and lysosomal acid lipase deficiency [cholesteryl ester storage disease and Wolman disease (WD)]. These diseases can cause significant liver problems ranging from asymptomatic hepatomegaly to cirrhosis and portal hypertension. Abnormal storage cells initiate hepatic fibrosis in sphingolipid disorders. Dyslipidemia causes micronodular cirrhosis in lipid storage disorders. These disorders must be keenly differentiated from other chronic liver diseases and non-alcoholic steatohepatitis that affect children and young adults. GD, Niemann-Pick type C, and WD also cause neonatal cholestasis and infantile liver failure. Genotype and liver phenotype correlation is variable in these conditions. Patients with LSD may survive up to 4-5 decades except for those with neonatal onset disease. The diagnosis of all LSD is based on enzymatic activity, tissue histology, and genetic testing. Enzyme replacement is possible in GD and Niemann-Pick types A and B though there are major limitations in the outcome. Those that progress invariably require liver transplantation with variable outcomes. The prognosis of Niemann-Pick type C and WD is universally poor. Enzyme replacement therapy has a promising role in cholesteryl ester storage disease. This review attempts to outline the natural history of these disorders from a hepatologist’s perspective to increase awareness and facilitate better management of these rare disorders.

Keywords: Lysosomal, Gaucher, Niemann-Pick, Wolman, Cholesteryl ester, Children

Core Tip: Lysosomal storage disorders have a multisystem involvement. Gaucher disease, Niemann-Pick disease, and lysosomal acid lipase deficiency (Wolman disease and cholesteryl ester storage disorder) may present with predominant liver dysfunction. Those with neonatal-onset, severe extrahepatic and multi-systemic presentations often have challenging outcomes. Enzyme replacement therapy and liver transplantation are encouraged in selected patients. Genetic tests and counseling are important aspects of disease management.