Fatty-Acid Oxidation Disorders Flashcards Preview

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Flashcards in Fatty-Acid Oxidation Disorders Deck (10):
1

VLCAD deficiency - enzyme/gene info

-Very long-chain acyl-coA dehydrogenase
-Catalyzes the first step of the beta-oxidation pathway
-Breaks down long-chain and very long-chain fatty acids (14 carbons or more)
-ACADVL gene
-Autosomal recessive inheritance
-Strong genotype/phenotype correlation - truncating mutations associated with NO residual enzyme activity
-Mild phenotype associated with residual enzyme activity and common p.Val283Ala mutation

2

VLCAD deficiency - phenotype

-3 phenotypes
Severe early-onset cardiac and multi-organ failure VLCAD deficiency:
-HCM or DCM, hepatomegaly, pericardial effusions, cardiac arrhythmias, hypoglycemia
-Lethality from cardiac symptoms
-No associated cognitive impairment

Hypoketotic hypoglycemic VLCAD deficiency:
-Hypoketotic hypoglycemia without associated cardiomyopathy
-Onset in early childhood

Late-onset episodic myopathic VLCAD deficiency:
-Most common phenotype
-Muscle cramps and pain
-Exercise intolerance
-Intermittent rhabdomyolysis
-Hypoglycemia may not be present

3

LCHAD deficiency - enzyme/gene info

-Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
-Breaks down long-chain fatty acids (13-21 carbons)
-HADHA gene
-Autosomal recessive inheritance
-Most people with LCHADD are homozygous for the common mutation c.1528G>C

4

LCHAD deficiency - phenotype

-Severe early-onset (infancy to 12 months)
-Hypoketotic hypoglycemia
-Metabolic acidosis
-Hepatic encephalopathy
-Cardiomyopathy and arrhythmia

5

MCAD deficiency - enzyme/gene info

-Medium-chain acyl-coA dehydrogenase deficiency
-Breaks down medium-chain fatty acids (6-12 carbons)
-ACADM gene
-Autosomal recessive inheritance
-No strong genotype/phenotype correlation
-Common p.Lys304Gly mutation

6

MCAD deficiency - phenotype

-Onset typically by age 2 (may not present until adulthood)
-Previously healthy child presents with:
-Hypoketotic hypoglycemia
-Vomiting
-Lethargy
-Seizures
-Hepatomegaly
-Can progress to coma/death

7

SCAD deficiency - enzyme/gene info

-Short-chain acyl-coA dehydrogenase deficiency
-Breaks down short-chain fatty acids (2-5 carbons)
-ACADS gene
-Autosomal recessive inheritance
-No strong genotype/phenotype correlation
-c.319C>T common mutation

8

Fatty Acid Oxidation Disorders - Treatment

-Avoid fasting for more than 12 hours
-Avoid illness - severe illness in LCHADD and VLCADD can trigger metabolic crisis, routine illness in MCAD and SCAD can trigger metabolic crisis
-Avoid high-fat diets
-Supplement calories with frequent feedings to maintain glucose levels
-Calorie supplementation for LCHADD and VLCADD through C7 (tripheptanoin) and MCT oil
-C7 can reverse/prevent cardiac symptoms in VLCADD patients

9

Fatty Acid Oxidation Disorders - Testing

-All disorders are part of NBS panels
-Acylcarnitine profile
-Urine organic acids can show dicarboxylic acidosis
-Enzyme activity analysis can be useful for VLCADD, but not MCAD/SCAD
-Molecular genetic testing

10

Other Fatty Acid Oxidation Disorders

-Carnitine Palmitoyltransferase I and II Deficiency (CPT I and CPTII) - cardiomyopathy, liver failure, seizures/coma
-Carnitine Transporter Deficiency - hypoglycemia, hepatomegaly, cardiac problems, hyperammonemia