Leigh syndrome-like MRI changes in a patient with biallelic HPDL variants treated with ketogenic diet

Area of Science:

• Biochemistry
• Genetics
• Neuroscience

Background:

• Biallelic variants in 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) are linked to progressive, incurable neurodegenerative disorders.
• These disorders manifest with symptoms including neonatal-onset leukoencephalopathy, severe neurodevelopmental delay, and spastic paraplegia.
• The precise physiological role of HPDL and its mitochondrial localization are under investigation.

Purpose of the Study:

• To report a novel case of HPDL-related neurological disease.
• To describe clinical and neuroimaging findings consistent with Leigh syndrome in an HPDL variant patient.
• To evaluate the therapeutic effect of a ketogenic diet in this condition.

Main Methods:

• Clinical case presentation.
• Neuroimaging analysis (MRI/CT).
• Genetic variant analysis for HPDL.
• Dietary intervention with a ketogenic diet.

Main Results:

• The patient presented with clinical and neuroimaging features characteristic of Leigh syndrome.
• Genetic analysis confirmed biallelic HPDL variants.
• Treatment with a ketogenic diet showed positive clinical response.

Conclusions:

• HPDL variants can cause neurological disease phenotypes overlapping with Leigh syndrome.
• A ketogenic diet may be a potential therapeutic strategy for HPDL-related neurological disorders.
• Further research is warranted to elucidate HPDL function and optimize treatment approaches.