1. Background

• pyruvate dehydrogenase (PDH) is a complex of 3 enzymes:
  • pyruvate decarboxylase
  • dihydrolipoyl transacetylase
  • dihydrolipoyl dehydrogenase
• pyruvate decarboxylase is the first enzyme in this PDH complex and is responsible for the oxidative decarboxylation of pyruvate to carbon dioxide and acetyl-CoA

2. Genetic Defect

• genetic defect -> decreased activity of pyruvate decarboxylase
• unable to convert pyruvate to acetyl-CoA -> build-up of pyruvate and lactic acid

1. Episodic

• spontaneous or triggered by stress, infections, or a high car-bohydrate meal
• occur at irregular intervals and last from days to weeks
• severity of symptoms depend on the level of residual pyruvate decarboxylase activity

2. Neonatal Onset

• no residual enzyme activity
• symptoms begin soon after birth
  • central hypoventilation
  • severe lactic acidosis
  • death in infancy

3. Infantile Onset

• low residual enzyme activity
• symptoms begin in early infancy
  • generalized weakness with areflexia
  • decreased level of consciousness
  • nystagmus

4. Childhood Onset

• moderate residual enzyme activity
• symptoms begin in early childhood
  • developmental delay
  • movement disorders
    • ataxia
    • chorea/choreoathetosis
  • dysarthria
  • lethargy
  • normal intelligence

1. Diagnosis

• reduced pyruvate decarboxylase activity in cultured fibroblasts, leukocytes, or muscle

2. Serum

• lactic acidosis
  • mildly elevated between episodes and markedly during an episode -> metabolic acidosis
• elevated pyruvate
• elevated alanine
• oral glucose tolerance test
  • hyperglycemia prolonged with elevated lactate

3. Cerebral Spinal Fluid

• elevated lactate

1. Diet

• ketogenic (high-fat) diet

2. Medications