Inborn Errors of Metabolism Practice Questions
19 free Inborn Errors of Metabolism practice questions for the USMLE Step 1. Tap an option to answer — you get instant feedback, the correct answer, and a detailed explanation for every question.
A newborn screening picks up elevated phenylalanine levels. Which enzyme deficiency is most consistent with this finding?
- A Tyrosine hydroxylase
- B Phenylalanine hydroxylase
- C Homogentisate oxidase
- D Branched-chain α-ketoacid dehydrogenase
Correct answer: Phenylalanine hydroxylase
A deficiency of phenylalanine hydroxylase prevents conversion of phenylalanine → tyrosine, leading to accumulation of phenylalanine characteristic of (PKU).
Which of the following clinical features is classically associated with untreated PKU?
- A Maple-syrup odor of urine
- B Sweaty-feet odor of urine
- C Musty or mousy odor of urine or skin
- D Fishy odor of urine
Correct answer: Musty or mousy odor of urine or skin
Untreated PKU often results in a characteristic “musty” (or “mousy”) odor of the skin, urine or breath due to elevated phenylalanine and its metabolites.
(MSUD) involves defective metabolism of which group of amino acids?
- A Aromatic amino acids (phenylalanine, tyrosine, tryptophan)
- B Sulfur-containing amino acids (methionine, cysteine)
- C Branched-chain amino acids (leucine, isoleucine, valine)
- D Basic amino acids (lysine, arginine, histidine)
Correct answer: Branched-chain amino acids (leucine, isoleucine, valine)
MSUD results from defective activity of the branched-chain α-ketoacid dehydrogenase complex, impairing breakdown of the branched-chain amino acids leucine, isoleucine and valine.
A neonate presents with poor feeding, irritability, and a sweet odor in urine. Which inborn error of metabolism is most likely?
- A Phenylketonuria (PKU)
- B Maple Syrup Urine Disease (MSUD)
- C Medium-chain acyl-CoA dehydrogenase deficiency (MCADD)
- D Galactosemia
Correct answer: Maple Syrup Urine Disease (MSUD)
The sweet (maple-syrup) odor of urine along with early neurologic symptoms is suggestive of MSUD, due to accumulation of branched-chain amino acids and their ketoacids.
Which of these is a common biochemical consequence of inborn errors of metabolism in amino-acid pathways?
- A Depletion of essentially all amino acids from the plasma pool
- B Accumulation of upstream substrates or toxic metabolites
- C Overproduction of ATP causing a hyperenergetic metabolic state
- D Markedly increased fatty acid oxidation as compensation
Correct answer: Accumulation of upstream substrates or toxic metabolites
Enzyme deficiencies in metabolic pathways often lead to inability to process substrates, resulting in their accumulation — sometimes as toxic metabolites — which underlies many inborn errors of metabolism.
A child with episodic hypoglycemia and accumulation of fatty-acid intermediates during fasting suggests a disorder in which metabolic pathway?
- A Amino acid catabolism
- B Fatty acid β-oxidation
- C Glycolysis
- D Urea cycle
Correct answer: Fatty acid β-oxidation
Fatty-acid β-oxidation disorders impair the body’s ability to generate energy from fats during fasting, leading to hypoglycemia and buildup of fatty-acid intermediates.
Which of the following is the most accurate general definition of an inborn error of metabolism (IEM)?
- A Inherited structural protein defects that cause immunodeficiency
- B Inherited enzyme defects that impair metabolic pathways
- C Chromosomal abnormalities producing major organ malformations
- D Acquired metabolic disturbances due to dietary deficiency states
Correct answer: Inherited enzyme defects that impair metabolic pathways
IEMs are genetic (often autosomal recessive) disorders caused by enzyme defects that disrupt biochemical pathways, resulting in accumulation of substrates or lack of necessary products.
Why are many inborn errors of metabolism (IEMs) detected via newborn screening?
- A They produce overt clinical symptoms only later in adulthood
- B They cause early accumulation of abnormal metabolites in blood or urine
- C They manifest solely as structural malformations of organs
- D They primarily raise adult-onset risks such as hypertension
Correct answer: They cause early accumulation of abnormal metabolites in blood or urine
Many IEMs result in accumulation of abnormal substrates or metabolites shortly after birth, which can be detected by blood or urine screening — allowing early diagnosis and management.
Which of the following metabolic disorders would most likely present with hyperammonemia due to impaired nitrogen disposal?
- A Maple Syrup Urine Disease (MSUD)
- B Urea cycle disorder
- C Medium-chain acyl-CoA dehydrogenase deficiency
- D Glycogen storage disease
Correct answer: Urea cycle disorder
Urea cycle disorders impair the body’s ability to convert toxic ammonia into urea for excretion, leading to hyperammonemia, a hallmark of these inborn errors.
A patient with an inborn error of metabolism affecting carbohydrate storage presents with severe fasting hypoglycemia and lactic acidosis. Which category does this most likely belong to?
- A Amino acidopathy such as phenylketonuria
- B A fatty acid oxidation disorder of beta-oxidation
- C Glycogen storage disease (glycogen metabolism disorder)
- D A urea cycle enzyme deficiency defect
Correct answer: Glycogen storage disease (glycogen metabolism disorder)
Glycogen storage diseases affect the ability to mobilize stored glycogen during fasting; impaired glycogenolysis or gluconeogenesis can lead to hypoglycemia and lactic acidosis.
Which of the following is true regarding inheritance and prevalence of most inborn errors of metabolism?
- A They are usually autosomal dominant and individually common
- B They are usually autosomal recessive: each rare but collectively frequent
- C They are X-linked and therefore affect only male children
- D They arise almost exclusively from new de novo mutations
Correct answer: They are usually autosomal recessive: each rare but collectively frequent
Most IEMs are inherited in an autosomal recessive fashion; although each disorder is individually rare, together they occur more commonly as a group.
Which of the following inborn errors of metabolism would classically present with a “sweaty-feet” odor of the body or urine?
- A Isovaleric acidemia
- B Phenylketonuria (PKU)
- C Maple Syrup Urine Disease (MSUD)
- D Medium-chain acyl-CoA dehydrogenase deficiency
Correct answer: Isovaleric acidemia
Isovaleric acidemia, a type of organic acidemia, is known to produce a characteristic sweaty-feet odor due to accumulation of isovaleric acid in body fluids.
In the context of inborn errors of metabolism, what is the primary benefit of early dietary management (e.g. restricted amino acid or sugar intake)?
- A To permanently cure the underlying enzyme deficiency itself
- B To prevent buildup of toxic substrates and reduce metabolic stress
- C To boost the cell's endogenous production of the missing enzyme
- D To increase overall calorie intake to support normal growth
Correct answer: To prevent buildup of toxic substrates and reduce metabolic stress
Dietary restriction prevents buildup of toxic upstream metabolites or reduces metabolic demands, thereby preventing organ damage and clinical complications, although it does not cure the genetic enzyme defect.
A patient with episodic metabolic decompensation, vomiting, acidosis, and elevated organic acids in urine likely has which class of IEM?
- A Amino acidopathy
- B Organic acidemia / aciduria
- C Glycogen storage disease
- D Urea cycle defect
Correct answer: Organic acidemia / aciduria
Organic acidemias (or acidurias) lead to accumulation of toxic organic acids, causing metabolic acidosis, vomiting, and metabolic decompensation, especially during catabolic stress.
Which inborn error of metabolism would you suspect in a child with intermittent hypoketotic hypoglycemia, especially during fasting or illness?
- A Glycogen storage disease type I (von Gierke)
- B Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
- C Phenylketonuria (PKU) due to PAH deficiency
- D Maple Syrup Urine Disease (MSUD) of branched-chain amino acids
Correct answer: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
MCAD deficiency impairs fatty acid β-oxidation; during fasting, the inability to oxidize fatty acids prevents ketone production, causing hypoketotic hypoglycemia, often with lethargy or seizures.
Why do many amino acid–metabolism IEMs result in neurologic deficits if untreated early in life?
- A Because amino acids serve as the main energy source for neurons
- B Because toxic amino acids or metabolites damage developing brain tissue
- C Because amino acids are entirely unable to cross the blood-brain barrier
- D Because they trigger massive lactic acidosis that selectively kills neurons
Correct answer: Because toxic amino acids or metabolites damage developing brain tissue
Toxic accumulation of amino acids or their metabolites can disrupt neurotransmitter balance or damage neural tissue — leading to developmental delay, intellectual disability or seizures seen in untreated amino acidopathies.
Which of the following best describes why IEMs may sometimes remain undiagnosed until adulthood in milder cases?
- A Because they affect only hair texture and skin pigmentation
- B Because partial enzyme function causes episodic or subtle symptoms
- C Because they invariably cause lethal disease in the neonatal period
- D Because they manifest only with very high-protein diets in adults
Correct answer: Because partial enzyme function causes episodic or subtle symptoms
Partial enzyme activity may suffice under normal conditions; milder IEMs can cause intermittent or subtle symptoms that only become overt under stress (illness, fasting) — delaying diagnosis until later.
Which of the following IEM categories involves inability to produce energy effectively from fats, especially during fasting, leading to hypoglycemia and possible metabolic crisis?
- A Amino acidopathies
- B Carbohydrate storage disorders
- C Fatty acid oxidation disorders
- D Urea cycle disorders
Correct answer: Fatty acid oxidation disorders
Fatty acid oxidation disorders impair breakdown of fatty acids for energy; during fasting or stress, patients cannot mobilize fat stores and may develop hypoglycemia, lethargy, or metabolic decompensation.
A newborn with elevated blood galactose after feeding develops jaundice, vomiting and liver dysfunction. This scenario best fits which IEM category?
- A Amino acidopathy of branched-chain amino acids
- B Carbohydrate (galactose) metabolism disorder
- C Mitochondrial fatty acid oxidation disorder
- D Urea cycle disorder with hyperammonemia
Correct answer: Carbohydrate (galactose) metabolism disorder
Galactosemia is a carbohydrate-metabolism inborn error; inability to metabolize galactose leads to accumulation of toxic metabolites causing liver dysfunction, jaundice, and failure to thrive in neonates.