J Inherit Metab Dis. 2025 Nov;48(6):e70100. doi: 10.1002/jimd.70100.
ABSTRACT
Liver transplantation (LTx) has become, over the years, an increasingly used therapeutic option in patients with inherited metabolic diseases (IMD). Initially performed for Tyrosinemia Type I and ornithine transcarbamylase deficiency, it now accounts as the second indication for pediatric transplants worldwide. The use of LTx has been extended to systemic metabolic disorders, in which a genetically normal liver can correct the defect by providing an enzyme replacement therapy that improves metabolic control and disease burden, reducing the risk of metabolic crises and neurological damage, allowing for the withdrawal, in most diseases, of dietary restrictions and specific medications. The temporal changes, mainly reflecting improved LTx management through a multidisciplinary approach, have provided excellent outcomes and long-term patient survival, shifting the paradigm from a lifesaving procedure to a life-improving treatment. However, challenges still exist, particularly, in systemic IMD due to the persistence of the underlying defect in extra-hepatic tissues. Immunosuppression, especially in organic acidurias, may lead to new, drug-related, neurotoxic risks. The new indications for transplantation should target endpoints that are not exclusively clinical, addressing major attention to the improvement of health-related quality of life issues. Protocols for managing LTx in IMD need to be harmonized, and future joint multicenter actions will fill these gaps and provide a uniform vision of this evolving scenario.
PMID:41070599 | DOI:10.1002/jimd.70100
