Pyruvate dehydrogenase complex deficiency

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.