Lipid Mobilization/Catabolism

Question 1

Medium Chain Acyl‐CoA
Dehydrogenase (MCAD)
Deficiency

Answer 1

- decreased B‐oxidation : specifically
of MCFA
-C8‐C10 acyl carinitines in
blood
-hypoglycemia: decreased use of
FA by peripheral tissues, increased
reliance on GLU for energy,
decreased ATP and Acetyl CoA to
activate gluconeogenesis
-hypoketonemia: decreased B‐
oxidation in liver, decreased
substrate for ketogenesis (acetyl
CoA)

Treatment
IV glucose
frequent feeding and high
carbohydrate, low fat diet
avoid fasting

Question 2

CPT Deficiency

Answer 2

CPT I‐hypoglycemia,
predominantly affects liver
-hypoglycemia
-decreased ketogenesis

CPT II‐cardiomyopathy and
muscle weakness (myopathic
form)
-muscle weakness,
-lipid deposits in skeletal muscle,
-prolonged exercise results in
myoglobinuria and elevated CK
levels in serum

Treatment- cease muscle activity, give glucose

Question 3

Jamaican Vomiting

Sickness

Answer 3

Enzyme Inhibition: MCAD

unripe ackee fruit contains
hypoglycin A‐inhibitor of MCAD

inhibition of B‐oxidation results in
profound hypoglycemia

-hypoglycemia
-vomiting (2‐6 hours after
ingestion)
-drowsiness (due to
hypoglycemia)
-coma
-death (if not immediately
recognized and treated)

Question 4

Zellweger Syndrome

Answer 4

Defective Oxidation of Very Long Chain Fatty Acids

-levels of C26 FA are increased

• affects liver and brain
• mental retardation
• hepatomegaly
• usually fatal in infants
• delayed develop milestones

*normal development: very long
chain FA are initially oxidized in
peroxisomes.The shortened FA is
then transported to the
mitochondria for further oxidation

Question 5

Refsum Disease

Answer 5

Enzyme Deficiency:
Peroxisomal Phytanyl CoA a‐
hydroxylase

-no a‐Oxidation of phytanic acid (in
peroxisomes)
-phytanate accumulates in tissues,
especially neurologic tissues
**which is a dietary
branched chain FA, predominant
in dairy products

• visual defects
• ataxia
• polyneuropathy
• skeletal manifestations

dietary restriction of branched
chain fatty acids‐‐not very
effective treatment

Question 6

omega (w)‐oxidation

Answer 6

MCAD Deficiency, defective B‐
oxidation

dicarboxylic acids found in
circulation and in urine

minor pathway for the oxidation
of fatty acids
w‐oxidation results in oxidation of
the w‐C atom of the FA, forming
dicarboxylic acid

Question 7

Carnitine Deficiency

Answer 7

carnitine uptake into tissues impaired
transport of long chain FA’s -> mitochondria is impaired
B-oxidation is decreased

Systemic carnitine deficiency
(early age presentation)
Hypoglycemia, hypoketonemia

Myopathic carnitine deficiency
(presents at later age)
muscle weakness and cardiomyopathy
Ck-MM & myoglobin in urine (indicates skeletal muscle damage)

Reduced serum carnitine

Question 8

Increased Ketogenesis during Starvation

Answer 8

decreased insulin/glucagon ration (activation of HSL)

Increased B-oxidation (High NADH/NAD ratio)

pyruvate shunted to gluconeogenesis

Acetyl Coa shunted toward ketogenesis (rather than TCA)