Fatty Acid Oxidation Disorders Flashcards
What is the inheritance pattern of fatty acid oxidation disorders (e.g., MCAD, LCHAD, CPT II Deficiency)?
Autosomal recessive
A 9-month-old boy is brought to the emergency department with lethargy and vomiting. The symptoms began after a febrile illness with decreased oral intake. On examination, he is hypotonic and drowsy. Blood work shows hypoglycemia, undetectable ketones, and mild hyperammonemia. Plasma acylcarnitine profile reveals elevated levels of medium-chain fatty acids. Which of the following is the most appropriate next step in management?
A) Administration of 10% dextrose intravenously
B) Administration of oral carnitine supplementation
C) Initiation of a ketogenic diet
D) Restriction of medium-chain fatty acids in the diet
E) Emergency plasmapheresis
Answer: A) Administration of 10% dextrose intravenously
Explanation: In MCAD deficiency, fasting leads to hypoglycemia without ketone production due to the inability to metabolize medium-chain fatty acids for energy. Administering IV dextrose immediately provides an alternative energy source, halting catabolism and preventing further hypoglycemia and metabolic crisis.
Incorrect Answers:
B) Oral carnitine supplementation is unnecessary in MCAD deficiency as carnitine levels are not primarily affected.
C) A ketogenic diet would exacerbate the condition since fatty acid oxidation is impaired.
D) While dietary restrictions are important long-term, immediate intervention with IV dextrose is critical during acute episodes.
E) Emergency plasmapheresis is not indicated for MCAD deficiency, as the condition can be managed with supportive care.
What is the pathophysiology of Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency?
Deficiency in medium-chain acyl-CoA dehydrogenase, leading to impaired breakdown of medium-chain fatty acids and hypoketotic hypoglycemia
What are the clinical features of MCAD Deficiency?
- the nonspecific findings are vomiting and lethargy.
- severe symptoms are cardiopulmonary collapse, seizures and coma.
- the most specific finding is hypoketotic hypoglycemia.
What triggers symptoms in MCAD and LCHAD deficiencies?
- Prolonged fasting.
- States of increased metabolic demand (e.g., infection, exercise).
What laboratory findings are typical of MCAD Deficiency?
- Metabolic acidosis.
- Liver specific findings: elevated AST/ALT, prolonged PT/aPTT, hypoglycemia and
hyperammonemia. - Low or absent ketones in blood and urine are extremely specific.
How is this MCAD managed acutely and chronically?
- Give IV dextrose (10%) in the acute setting.
- Always avoid fasting states for long-term management.
What are the known complications that can result from MCAD?
- encephalopathy
- fatty liver disease and impaired liver function
- if not managed, death can occur
A 2-year-old girl presents with recurrent vomiting, lethargy, and muscle weakness. Her symptoms worsen during illnesses. Physical examination reveals hepatomegaly. Laboratory findings include hypoglycemia, low ketones, elevated liver enzymes, and lactic acidosis. Plasma acylcarnitine profile shows elevated long-chain acylcarnitines. Her mother had preeclampsia and HELLP syndrome during pregnancy. What dietary modification would best prevent future episodes?
A) Diet high in long-chain fatty acids
B) Supplementation with medium-chain fatty acids
C) Increased protein intake with carnitine supplementation
D) Total parenteral nutrition (TPN)
E) Restriction of short-chain fatty acids
Answer: Supplementation with medium-chain fatty acids
Explanation: In LCHAD deficiency, long-chain fatty acids cannot be metabolized, leading to toxic intermediates. Medium-chain fatty acids bypass the enzyme block and serve as an alternative energy source.
Incorrect Answers:
A) Long-chain fatty acids exacerbate symptoms by increasing the accumulation of toxic intermediates.
C) Increased protein intake is not the primary treatment for LCHAD deficiency. Carnitine supplementation is not typically required in this disorder.
D) TPN is unnecessary for long-term management and is not practical for preventing episodic crises.
E) Short-chain fatty acids are not affected in LCHAD deficiency and do not need restriction.
What is the pathophysiology of Long-Chain Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency?
Deficiency in long-chain hydroxyacyl-CoA dehydrogenase, leading to accumulation of toxic fatty acid intermediates and hypoketotic hypoglycemia.
This disorder can cause many issues from growth stunting, myopathy, cardiomyopathy, liver disease, and rhabdomyolysis.
What complications are associated with LCHAD Deficiency during pregnancy?
Pregnancy-associated disorders like preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy
What accumulates in the urine in LCHAD Deficiency?
3-hydroxydicarboxylic acids in urine
(urine is very acidic due to hydroxydicarboxylic acids and lactic acid)
Other lab findings: metabolic acidosis, hypoglycemia, hyperammonemia, low ketones in blood and urine (due to no fatty acid oxidation)
How is LCHAD deficiency normally discovered?
Newborn screening
Genetic testing for HADHA gene variant
A 6-month-old boy is brought to the clinic for poor weight gain and lethargy. His parents report recurrent episodes of vomiting and weakness, especially when the baby skips a meal. Examination reveals hepatomegaly and hypotonia. Laboratory findings show hypoketotic hypoglycemia, hyperammonemia, and very low plasma carnitine levels. What is the most appropriate treatment to prevent future episodes?
A) Frequent feeding with a high-protein diet
B) Oral carnitine supplementation and avoidance of fasting
C) Dietary supplementation with long-chain triglycerides
D) Initiation of a ketogenic diet
E) Emergency IV glucagon during episodes
Answer: Oral carnitine supplementation and avoidance of fasting
Explanation: Primary Carnitine Deficiency results from impaired carnitine transport into cells, leading to reduced fatty acid metabolism. Oral carnitine supplementation replenishes intracellular stores and facilitates fatty acid transport, while frequent meals prevent hypoglycemia during fasting. Acute management calls for 10% dextrose (IV).
Incorrect Answers:
A) High-protein diets are not indicated, as the primary issue is defective fatty acid oxidation, not protein metabolism.
C) Long-chain triglycerides are poorly metabolized in this condition and may worsen symptoms.
D) A ketogenic diet would worsen hypoketotic hypoglycemia due to impaired fatty acid metabolism.
E) IV glucagon treats hypoglycemia by mobilizing glycogen but does not address the underlying carnitine deficiency.
What is the underlying defect in Primary Carnitine Deficiency?
Defective carnitine transporter, leading to impaired entry of long-chain fatty acids into mitochondria
