Introduction to Inborn Errors of Metabolism

Question 1

What can trigger episodes of acute metabolic decompensation?

Answer 1

surgery
illness
vaccines

Question 2

What cause hyperammonemia?

Answer 2

urea cycle disorders (most common)
organic acidemias
fatty acid oxidation disorders
mitochondrial disorders
other non-IEM causes (eg. liver failure or drugs like valproic acid)

Question 3

What are metabolic causes for elevated lactate?

Answer 3

primary mitochondrial disorders
pyruvate dehydrogenase/pyruvate carboxylase deficiency
long-chain fatty acid oxidation disorders
organic acidurias
disorders of biotin metabolism
glycogen storage diseases
gluconeogenesis disorders

Question 4

What are non-metabolic causes for elevated lactate?

Answer 4

inadequate O2 delivery and anaerobic metabolism
hypoxia
shock
sepsis
drugs and alcohol intoxication
tourniquet while drawing blood

Question 5

What blood gas levels are observed in organic acidemias?

Answer 5

low pH (acidosis)
Low pCO2 (respiratory compensation secondary)
Low HCO3 (bicarb)
*defined as low bicarb and high anion gap (cannot be an IEM if this is not the case)

Question 6

What blood gas levels are observed in urea cycle disorders?

Answer 6

High pH (alkalosis)
Low pCO2 (respiratory alkalosis)
Normal to high HCO3 (bicarb)

Question 7

What kinds of conditions can Plasma Amino Acid (PAA) test be used to identify?

Answer 7

aminoacidopaties
hyperammonemia
if there is an IEM, this will be significantly elevated

Question 8

What kinds of conditions can Acylcarnitine Profiles (ACP) be used to identify?

Answer 8

fatty acid oxidation defects (primarily)
organic acidurias
make sure to look at ratios and elevation status

Question 9

Why can carnitine be used to identify IEMs?

Answer 9

primary deficiency indicates problem in the transport of carnitine directly
secondary deficiency indicates too many metabolites for carnitine to bind

Question 10

What kinds of conditions are indicated by elevated CPK?

Answer 10

fatty acid oxidation disorders
mitochondrial disorders
glycogen storage diseases