Ketogenic Diet for KARS-Related Mitochondrial Dysfunction and Progressive Leukodystrophy.

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Mutations in the KARS gene, encoding lysyl-tRNA synthetase, disrupt protein synthesis and can lead to progressive leukodystrophies with severe neurological impairment and early mortality.
• Currently, no disease-modifying therapies exist for KARS-related leukodystrophy, with treatment limited to supportive care.

Observation:

• A 5-year-old male presented with asymmetrical leukodystrophy, confirmed mitochondrial dysfunction (elevated brain lactate, reduced fibroblast oxygen consumption), cerebral calcification, and congenital deafness.
• The patient exhibited psychomotor regression characteristic of KARS-related leukodystrophy.

Findings:

• A therapeutic trial involving a ketogenic diet and comprehensive vitamin supplementation was initiated to address the underlying mitochondrial dysfunction.
• The patient demonstrated significant alleviation of psychomotor regression and partial recovery of abilities within four months of treatment.
• No significant adverse effects were observed during the intervention period.

Implications:

• This case report suggests that a ketogenic diet combined with vitamin supplementation may represent a potential disease-modifying therapy for KARS-related leukodystrophy.
• Further research is warranted to validate these findings and explore the mechanisms underlying this therapeutic response in patients with KARS mutations.