Skip to Main Content

++

FATTY ACID OXIDATION DISORDERS

++

GENERAL PRINCIPLES

++

Class of metabolic diseases in which enzyme deficiencies in mitochondrial fatty acid import or b-oxidation limit the ability of mitochondria to use fat as an energy source.

++

EPIDEMIOLOGY

++

  • Overall incidence about 1:10,000; autosomal recessive inheritance

  • Medium-chain acyl CoA dehydrogenase (MCAD) deficiency is the most common fatty acid oxidation (FAO) defect

++

PATHOPHYSIOLOGY

++

Most significant danger is hypoketotic hypoglycemia, leading to failure of multiple organ systems. General considerations:

++

  • FAO provides energy for heart and liver at baseline, and for skeletal muscle during prolonged exercise. FAO produces ketones used by brain as energy source during prolonged fast

  • FAO supports gluconeogenesis by providing ATP, acetyl CoA, and reduced electron carriers

  • Risk for hypoketotic hypoglycemia highest when relying on FAO for energy (e.g., prolonged fast, infection)

  • Buildup of long-chain fats is toxic to liver, heart, and muscle cells and can result in acute liver injury, cardiomyopathy, or episodic rhabdomyolysis in times of catabolism or excess fat consumption

++

CLINICAL MANIFESTATIONS

++

Varies with syndrome but initial presenting symptoms include hypoketotic hypoglycemia; neonatal neurologic symptoms; coma; Reye-like syndrome; cardiac arrhythmia; cardiomyopathy; sudden death, rhabdomyolysis

++

DIAGNOSTICS

++
Decompensated Patient
++

  • Dextrose stick; serum Na, K, Cl, HCO3, hepatic function panel, ammonia, uric acid. CPK, plasma acylcarnitine profile, total and free carnitine

  • Blood gas if concern for metabolic acidosis

  • Urine for ketones, myoglobin (if blood in U/A), and organic acid profile

  • Consider ECG, echocardiography

++
Other Studies
++

  • Acylcarnitine profiles performed in newborn screening programs have identified FAO disorders (FAOD) in many presymptomatic patients

  • Mutation (DNA) diagnosis

  • Enzyme assays on fibroblasts for some disorders

++

MANAGEMENT

++
Acute
++

Goal is to reverse hypoglycemia immediately, to curtail anabolism, and to treat associated morbidities:

++

  • Place widest gauge IV catheter immediately. Some patients require central access to maintain high dextrose infusion rates

  • Dextrose bolus (initial bolus of 2 cc/kg with D10; bolus may need to be repeated in older patients), then start dextrose infusion with D10 plus electrolytes at 1.5 × maintenance rate. Insulin surge after dextrose infusion inhibits further lipolysis

  • Saline boluses if dehydrated, but should not delay establishing euglycemia

  • Do not use intralipids

  • Early consultation with biochemical geneticist or other specialist

++
Chronic
++

  • Carnitine supplementation for primary carnitine deficiency (e.g., carnitine transporter defect [CTD]). Use in other FAODs is typically done, but benefit is controversial

  • For disorders affecting long-chain FAO, low fat, high carbohydrate diet, limit long-chain fatty acid intake. Diet is unrestricted in medium/short-chain disorders

  • For disorders affecting long-chain FAO, supplement diet with medium-chain triglycerides (2–3 g/kg/day for infants; 1 g/kg/day in older children)

  • Strategies to avoid hypoglycemia include frequent or continuous feeds, evening snacks ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.