[Research advances in Infantile liver failure syndrome]

Area of Science:

• Pediatric Hepatology
• Clinical Genetics
• Molecular Medicine

Background:

• Pediatric acute liver failure (PALF) is a rare condition with complex and often indeterminate etiology.
• Recurrent acute liver failure (RALF) in infants, termed Infantile Liver Failure Syndrome (ILFS), is increasingly linked to genetic metabolic defects.
• Understanding the genetic basis of ILFS is crucial for diagnosis and management.

Purpose of the Study:

• To systematically review the clinical, genetic, and therapeutic aspects of three ILFS subtypes (ILFS1, ILFS2, ILFS3).
• To enhance early clinical recognition and guide precise interventions for ILFS.
• To provide a reference for prognosis evaluation across different ILFS subtypes.

Main Methods:

• Systematic literature review focusing on clinical phenotypes, molecular genetics, diagnostic strategies, and treatments.
• Analysis of high-throughput sequencing data to identify genetic causes of ILFS.
• Synthesis of information on aminoacyl-tRNA synthetase defects (ILFS1), vesicular transport disorders (ILFS2), and autophagy abnormalities (ILFS3).

Main Results:

• ILFS subtypes share a phenotype of RALF triggered by fever or infection.
• Distinct molecular mechanisms underlie ILFS1 (aminoacyl-tRNA synthetase defects), ILFS2 (vesicular transport disorders), and ILFS3 (autophagy abnormalities).
• Advancements in genetic sequencing have unveiled these specific genetic causes for previously indeterminate PALF cases.

Conclusions:

• ILFS represents a spectrum of genetic disorders presenting as recurrent acute liver failure in children.
• Accurate diagnosis requires understanding the distinct molecular pathways of ILFS subtypes.
• Improved early recognition and targeted therapies are essential for managing ILFS and improving patient prognosis.