Novel imaging findings in pyruvate dehydrogenase complex (PDHc) deficiency-Results from a nationwide population-based...

Area of Science:

• Neuroimaging
• Metabolic Disorders
• Genetics

Background:

• Pyruvate dehydrogenase complex (PDHc) deficiency exhibits a wide range of clinical and radiological manifestations, complicating diagnosis and management.
• Early diagnosis of PDHc deficiency is crucial for timely intervention with a ketogenic diet.

Purpose of the Study:

• To characterize the spectrum of brain MRI findings in genetically confirmed PDHc deficiency.
• To identify potential MRI clues for early diagnosis and monitoring of PDHc deficiency.
• To analyze the evolution of MRI changes in relation to lesion type and developmental stage.

Main Methods:

• Retrospective analysis of 62 brain MRI investigations from 34 patients with genetically confirmed PDHc deficiency.
• Classification of lesions based on developmental stage (prenatal developmental, prenatal clastic, postnatal clastic).
• Correlation of MRI findings with genetic mutations (PDHA1, PDHX, DLAT, PDHB).

Main Results:

• Common MRI findings included agenesis/hypoplasia of corpus callosum, ventriculomegaly, and Leigh-like lesions.
• Diverse lesion types were observed, including prenatal developmental, prenatal clastic, and postnatal clastic.
• The simultaneous presence of lesions from different developmental phases emerged as a significant indicator of PDHc deficiency.

Conclusions:

• Brain MRI reveals a broad spectrum of abnormalities in PDHc deficiency, varying by lesion type and genetic cause.
• The presence of multiple, distinct lesion types on MRI, reflecting different brain development phases, is a key diagnostic clue for PDHc deficiency.
• These findings underscore the importance of comprehensive MRI analysis for diagnosing and managing PDHc deficiency.