Fatty Acid Oxidation Disorders (FAOD): When Mitochondria Can't Burn Fat for Energy

If mitochondria can utilize fatty acids but not amino acids for energy, a fatty acid oxidation disorder (FAOD) is suspected. These are autosomal recessive defects in mitochondrial β-oxidation or carnitine transport.

Common FAODs

• MCADD (medium-chain acyl-CoA dehydrogenase deficiency): Most common (~1:15,000). Presents in infancy with hypoketotic hypoglycemia, lethargy, liver dysfunction after fasting/illness.
• VLCADD, LCHADD, CPT I/II deficiency: Variable severity; cardiac, hepatic, myopathic forms.

Pathophysiology

During fasting, fatty acids are the primary fuel. Blocked β-oxidation → inability to generate ketones and ATP → hypoglycemia, metabolic acidosis, hyperammonemia, rhabdomyolysis, cardiomyopathy.

Diagnosis

• Newborn screening (acylcarnitine profile by tandem MS).
• Confirmatory: genetic testing, enzyme assay, fibroblast studies.

Management

• Avoid fasting: Frequent feeds, cornstarch at night (infants/children).
• Low-fat, high-carb diet: MCT oil supplementation (bypasses long-chain defects).
• Carnitine: For carnitine transporter defects; controversial for others.
• Emergency protocol: IV dextrose 10% at 1.5× maintenance at first sign of illness; avoid fasting >4–6 hrs (age-dependent).

Prognosis

With early diagnosis and strict metabolic management, most patients achieve normal development and lifespan. Undiagnosed FAOD can cause sudden infant death or severe disability.