Fatty Acid Oxidation Disorders

Question 1

General Features of FAO Disorders

Answer 1

Inheritance: Autosomal recessive
Signs and symptoms:
•Fasting intolerance – body is not able to utilize fat for energy
oRecurrent vomiting, lethargy, coma
•HYPOKETOTIC HYPOGLYCEMIA
oMost common genetic cause of hypoketotic hypoglycemia
•Low carnitine levels on labs
•Long chain defects (LCHAD, VLCAD) exhibit cardiomyopathy and generalized myopathy

Question 2

FAO: Types

Answer 2

Types:
•VLCAD – Very-long chain acyl-coA dehydrogenase deficiency
•LCHAD – long-chain 3-hydroxyacyl-coA dehydrogenase deficiency
•MCAD – medium chain acyl-coA dehydrogenase deficiency
oMCAD IS THE MOST COMMON FAO DISORDER
•SCAD – short-chain acyl-coA dehydrogenase deficiency
oOnly FAO that does not present with hypoketotic hypoglycemia

Question 3

FAO: Labs and treatment

Answer 3

Labs
•Urine organice acids, acylcarnitine profile, acylglycines
oMay only be abnormal during crises
•Molecular genetic confirmation
Treatment
•Avoid periods of prolonged fasting
•Avoid high fat diets
•Illness is a trigger for crises
•Frequent feedings to maintain glucose levels
•MCT (medium-chain-triglycerides) oil can provide calorie supplementation to individuals with LCHAD and VLCAD (they can break down medium chains, but not long chains)
•Trihepatonoin (C7) can reverse or prevent cardiomyopathy in individuals with LCHAD or VLCAD
•

Question 4

X-linked Adrenoleukodystrophy

Peroxisomal

Answer 4

Inheritance: X-linked recessive
Gene: ABCD1
Childhood Cerebral Form:
•Onset between 4-8 years of age
•Progressive neurodegenerative decline
•Behavioral and learning deficits
•Seizures
•Adrenocortical dysfunction
•Total disability and early death 6 months – 2 years after onset

Question 5

Adrenomyeloneuropathy

Peroxisomal

Answer 5

Adrenomyeloneuropathy
•Onset in 20s
•Progressive stiffness and weakness in the legs
•Abnormal sphincter control
•Sexual dysfunction
•Adrenocortical dysfunction
•Neuropathy
•40-50% have brain MRI abnormalities (leukodystrophy)
•10-20% of those with leukodystrophy have severely progressive cognitive decline and early death

Question 6

Addison’s Disease (Isolated)

Answer 6

Addison’s Disease (Isolated)
•Adrenal insufficiency in the absence of MRI/brain anomalies
•Increased skin pigmentation from excess ACTH

Affected females
•Majority of symptomatic females exhibit mild myelopathy/sensory changes in lower extremities
•A small portion show cognitive decline
•Usually do not show adrenocortical dysfunction

Question 7

XL ALD treatment

Answer 7

Treatment
•Corticosteroid replacement therapy is necessary and lifesaving for adrenal insufficiency
X
•Hematopoeitic stem cell transplant may rescue brain involvement but is risky and limited to individuals with brain involvement but normal cognitive function