Muscle involvement in pyruvate dehydrogenase complex (PDHC) deficiency

Area of Science:

• Biochemistry
• Neurology
• Genetics

Background:

• Pyruvate dehydrogenase complex (PDHC) deficiency is a rare inherited metabolic disorder.
• It leads to lactic acidosis and can cause significant neurological impairment.

Observation:

• Two female patients, a 13-month-old infant and a 6-year-old, presented with developmental delay, lactic acidosis, visual disturbance, and epileptic fits.
• Muscle biopsies revealed markedly decreased PDHC activity (16% of normal) in both patients.
• Histochemistry showed disorganized muscle fiber networks, increased nonspecific esterase activity, and basophilic fibers, but lacked ragged-red fibers and lipid accumulation.

Findings:

• Electron microscopy showed mostly normal mitochondria, with focal subsarcolemmal aggregates of mildly enlarged mitochondria.
• Morphometric analysis did not reveal significant differences in mean mitochondrial size or mitochondrial volume percentage compared to controls.
• These findings suggest specific mitochondrial alterations secondary to PDHC deficiency.

Implications:

• This study highlights the diagnostic utility of muscle biopsy in identifying PDHC deficiency.
• Understanding these specific muscle histopathology findings aids in diagnosing and managing patients with this condition.
• Further research into the pathomechanisms of mitochondrial changes in PDHC deficiency is warranted.