MRI in LARS1 deficiency-Spectrum, patterns, and correlation with acute neurological deterioration.

Area of Science:

• Genetics and Neurology
• Pediatric Medicine
• Metabolic Disorders

Background:

• Leucine aminoacyl tRNA-synthetase 1 (LARS1) deficiency, also known as infantile liver failure syndrome type 1 (ILFS1), presents a complex multisystemic phenotype.
• This includes acute liver failure (ALF) often triggered by fever, chronic neurological deficits, and recurrent encephalopathic episodes.

Purpose of the Study:

• To systematically analyze cranial MRI findings and neurological phenotypes in individuals with LARS1 deficiency.
• To better characterize the encephalopathic episodes and associated neuroimaging changes.

Main Methods:

• A retrospective analysis of 35 cranial MRI scans from 13 individuals diagnosed with LARS1 deficiency.
• Correlation of MRI findings with neurological phenotype, including developmental delay, seizures, and encephalopathic episodes.

Main Results:

• All individuals exhibited developmental delay, and 10 out of 13 had seizures.
• Encephalopathic episodes, often linked to infections, presented with seizures and reduced consciousness, typically resolving after treatment.
• Characteristic MRI findings during acute encephalopathy included deep gray matter and brainstem abnormalities, differentiating it from other metabolic encephalopathies.

Conclusions:

• Deep gray matter and brainstem changes on MRI are distinctive features of encephalopathy in LARS1 deficiency.
• Infections, particularly influenza, may precipitate severe episodes, highlighting the importance of fever management and vaccination.
• Understanding these characteristic neuroimaging patterns aids in diagnosing and managing LARS1 deficiency.