• Definition: inherited genetic disorder characterized by impaired pyruvate metabolism
• Inheritance: X-linked recessive or autosomal recessive
• Pathophysiology
  • Why is it called pyruvate dehydrogenase? Because it takes the hydrogen from carbon and thus oxidizing it.
  • Absent pyruvate dehydrogenase complex (PDC) → impaired conversion of pyruvate to acetyl-CoA → reduced production of citrate → impaired citric acid cycle → energy deficit (especially in the CNS) → neurological dysfunction
  • Excess pyruvate is further metabolized in the Cahill cycle to the following
    • Lactate via lactate dehydrogenase
    • Alanine via alanine aminotransferase
• Clinical features
  • Onset: early neonatal period
  • Poor feeding, lethargy
  • Tachypnea
  • Developmental delay
  • Progressive neurological symptoms (e.g., seizures)
• Diagnostics
  • ↑ Lactate (lactic acidosis) and pyruvate in serum
  • ↑ Alanine in serum and urine
• Treatment
  • Acute: correction of acidosis
  • Long-term: ketogenic diet
    • High in fat, low in carbohydrates
    • High in ketogenic amino acids (lysine and leucine)
    • Avoidance of glucogenic acids (e.g., valine)
    • Avoid glucogenic amino acids: Methionine, histidine, valine.