Disorders of branched-chain amino acids (MSUD) US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Disorders of branched-chain amino acids (MSUD). These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 1: A 22-year-old man comes to the physician for a routine physical examination. He feels well. He has no history of major medical illness and takes no medications. His vital signs are within normal limits. Examination shows no abnormalities. Laboratory studies, including a complete blood count and a standard electrolyte panel, are within normal limits. Urine dipstick is negative for glucose; a reducing substance test result of the urine is positive. Which of the following is the most appropriate dietary recommendation for this patient?
- A. Eliminate galactose and lactose
- B. Eliminate fructose and sucrose
- C. Increase intake of ketogenic amino acids
- D. Decrease purine intake
- E. No changes needed (Correct Answer)
Disorders of branched-chain amino acids (MSUD) Explanation: ***No changes needed***
- The positive urine reducing substance test with negative urine glucose in an otherwise healthy individual often indicates **essential fructosuria**, a benign condition.
- Essential fructosuria is caused by a deficiency in **fructokinase** and does not require any dietary modifications.
*Eliminate galactose and lactose*
- This recommendation would be appropriate for **galactosemia**, a condition where the body cannot properly metabolize galactose.
- Galactosemia typically presents with more severe symptoms in infancy, such as **failure to thrive**, **jaundice**, and **cataracts**, which are not present here.
*Eliminate fructose and sucrose*
- This is the recommended diet for **hereditary fructose intolerance**, a more severe disorder involving a deficiency of **aldolase B**.
- Hereditary fructose intolerance would lead to symptoms like **hypoglycemia**, **vomiting**, and **liver damage** upon ingestion of fructose, which are absent in this case.
*Increase intake of ketogenic amino acids*
- This dietary approach is typically used for conditions like **pyruvate dehydrogenase complex deficiency** or **glucose transporter type 1 deficiency syndrome (Glut1 deficiency)**.
- These conditions involve metabolic crises or neurological symptoms that are not relevant to the patient's presentation.
*Decrease purine intake*
- A low-purine diet is recommended for conditions associated with **hyperuricemia**, such as **gout** or **Lesch-Nyhan syndrome**.
- There is no indication of elevated uric acid levels or symptoms related to purine metabolism in this patient.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 2: A 3-day-old female infant presents with poor feeding, lethargy, vomiting after feeding, and seizures. Labs revealed ketoacidosis and elevated hydroxypropionic acid levels. Upon administration of parenteral glucose and protein devoid of valine, isoleucine, methionine, and threonine, and carnitine, the infant began to recover. Which of the following enzymes is most likely deficient in this infant?
- A. Branched-chain ketoacid dehydrogenase
- B. Propionyl-CoA carboxylase (Correct Answer)
- C. Cystathionine synthase
- D. Phenylalanine hydroxylase
- E. Homogentisate oxidase
Disorders of branched-chain amino acids (MSUD) Explanation: ***Propionyl-CoA carboxylase***
- The presence of **ketoacidosis** and elevated **hydroxypropionic acid** levels is characteristic of propionic acidemia, which is caused by a deficiency in **propionyl-CoA carboxylase**.
- The therapeutic benefit from a diet restricted in **valine, methionine, threonine**, and **isoleucine** (precursors of propionyl-CoA) along with carnitine supplementation further supports this diagnosis.
*Branched-chain ketoacid dehydrogenase*
- A deficiency in this enzyme leads to **Maple Syrup Urine Disease**, characterized by elevated **branched-chain ketoacids** and associated with a distinctive sweet odor in urine.
- While it causes neurotoxicity and poor feeding, the specific finding of elevated **hydroxypropionic acid** points away from this diagnosis.
*Cystathionine synthase*
- Deficiency in **cystathionine synthase** causes **homocystinuria**, leading to elevated **homocysteine** levels.
- Symptoms include developmental delay, ectopia lentis, and skeletal abnormalities, but not typically elevated **hydroxypropionic acid** or severe neonatal ketoacidosis in this manner.
*Phenylalanine hydroxylase*
- This enzyme is deficient in **phenylketonuria (PKU)**, resulting in high levels of **phenylalanine** and its metabolites.
- PKU is typically associated with intellectual disability, seizures, and a musty odor, but not ketoacidosis or elevated **hydroxypropionic acid**.
*Homogentisate oxidase*
- A deficiency in this enzyme causes **alkaptonuria**, characterized by the accumulation of **homogentisic acid**.
- This condition is usually benign in infancy, primarily manifesting as dark urine upon standing and later developing into ochronosis and arthritis, without acute neonatal ketoacidosis or elevated **hydroxypropionic acid**.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 3: On a medical trip to Nicaragua, you observe a sweet odor in the cerumen of a 12-hour-old female newborn. Within 48 hours, the newborn develops ketonuria, poor feeding, and a sweet odor is also noticed in the urine. By 96 hours, the newborn is extremely lethargic and opisthotonus is observed. In order to prevent a coma and subsequent death, which of the following amino acids is one of those that should be withheld from this newborn's diet?
- A. Methionine
- B. Valine (Correct Answer)
- C. Phenylalanine
- D. Threonine
- E. Tyrosine
Disorders of branched-chain amino acids (MSUD) Explanation: ***Valine***
- The clinical presentation with a **sweet odor in cerumen** and urine, followed by **ketonuria**, poor feeding, lethargy, and opisthotonus, is highly characteristic of **Maple Syrup Urine Disease (MSUD)**.
- MSUD is an autosomal recessive disorder caused by a deficiency in the **branched-chain alpha-keto acid dehydrogenase complex (BCKDC)**, which is responsible for the metabolism of the branched-chain amino acids (BCAAs): **leucine, isoleucine, and valine**. Therefore, restricting these amino acids from the diet is crucial.
*Methionine*
- **Methionine** is an essential amino acid, but its dietary restriction is primarily associated with conditions like **homocystinuria**, not MSUD.
- The deficiency in MSUD specifically impacts the branched-chain amino acid pathway, not the methionine metabolism pathway.
*Phenylalanine*
- **Phenylalanine** is restricted in the diet of individuals with **phenylketonuria (PKU)**, a different inborn error of metabolism.
- PKU is characterized by the inability to metabolize phenylalanine to tyrosine, leading to its accumulation and neurotoxicity, with different clinical features than described.
*Threonine*
- **Threonine** is a different essential amino acid and is not one of the branched-chain amino acids whose catabolism is impaired in MSUD.
- Restricting threonine would not directly address the metabolic defect seen in MSUD.
*Tyrosine*
- **Tyrosine** is a non-essential amino acid that becomes essential in conditions like **phenylketonuria (PKU)**, where it cannot be synthesized from phenylalanine.
- It is not directly implicated in the pathogenesis or dietary management of MSUD.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 4: A 4-day-old boy is brought to the physician by his mother because of vomiting, irritability, and poor feeding. Pregnancy and delivery were uncomplicated. Physical examination shows increased muscle tone in all extremities. He appears lethargic. His diapers emit a caramel-like odor. Urine studies are positive for ketone bodies. Supplementation of which of the following is most likely to improve this patient's condition?
- A. Tyrosine
- B. Cysteine
- C. Tetrahydrobiopterin
- D. Thiamine (Correct Answer)
- E. Leucine
Disorders of branched-chain amino acids (MSUD) Explanation: ***Thiamine***
- This clinical scenario describes an infant with **vomiting, irritability, poor feeding, increased muscle tone, lethargy, and a caramel-like odor in the urine**, along with **ketone bodies in the urine**. These are classic signs of **Maple Syrup Urine Disease (MSUD)**.
- MSUD is caused by a deficiency in the **branched-chain alpha-keto acid dehydrogenase complex (BCKDC)**, an enzyme that requires **thiamine** as a cofactor. In some cases, high-dose thiamine supplementation can improve enzyme activity and alleviate symptoms.
*Tyrosine*
- **Tyrosine** is an amino acid. Disorders of tyrosine metabolism, such as tyrosinemia, present with liver dysfunction, renal tubulopathy, and neurological crises, but typically do not involve a caramel-like odor or respond to thiamine.
- Tyrosine supplementation is not indicated for MSUD and would not improve the patient's condition.
*Cysteine*
- **Cysteine** is a sulfur-containing amino acid. Disorders involving cysteine metabolism, like homocystinuria, are characterized by ocular, skeletal, vascular, and neurological abnormalities.
- There is no direct role for cysteine supplementation in treating MSUD, and it would not address the underlying enzymatic defect.
*Tetrahydrobiopterin*
- **Tetrahydrobiopterin (BH4)** is a cofactor for several enzymes involved in amino acid metabolism, particularly in the synthesis of neurotransmitters and the metabolism of phenylalanine.
- BH4 deficiency causes phenylketonuria-like symptoms or other neurological issues, but not MSUD, and it would not address the BCKDC deficiency.
*Leucine*
- **Leucine** is one of the branched-chain amino acids (BCAAs) that accumulate in MSUD due to the defective BCKDC enzyme.
- Supplementing leucine would worsen the patient's condition by increasing the toxic BCAA levels, as the body cannot properly metabolize it.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 5: A 2-month-old boy is brought to his pediatrician’s office to be evaluated for new onset seizures and poor weight gain. The patient’s father says he is unable to track with his eyes and is unresponsive to verbal stimuli. The patient is hypotonic on physical exam. Further studies show elevated serum lactate levels and elevated levels of alanine and pyruvate. Family history reveals that several distant family members suffered from neurological diseases and died of unknown causes at a young age. Which of the following amino acids should be increased in this patient’s diet?
- A. Isoleucine
- B. Valine
- C. Arginine (Correct Answer)
- D. Leucine
- E. Methionine
Disorders of branched-chain amino acids (MSUD) Explanation: ***Arginine***
- The symptoms of **seizures, developmental delay, hypotonia, and elevated lactate/pyruvate** levels, along with a family history of early deaths, are highly suggestive of a **mitochondrial disorder**, specifically **pyruvate dehydrogenase complex (PDC) deficiency**.
- **Arginine** supplementation is used in certain **mitochondrial disorders** to enhance **nitric oxide (NO) production**, which improves **endothelial function and tissue perfusion**. While the primary treatment for PDC deficiency is a **ketogenic diet** and cofactor supplementation (thiamine, lipoic acid), among the amino acid options listed, arginine has supportive evidence in mitochondrial cytopathies.
- Arginine may help counteract **endothelial dysfunction** and improve oxygen delivery to tissues affected by mitochondrial impairment.
*Isoleucine*
- **Isoleucine** is a **branched-chain amino acid (BCAA)** that is catabolized to produce acetyl-CoA and succinyl-CoA for energy.
- In **PDC deficiency**, the problem is the conversion of **pyruvate to acetyl-CoA**, not BCAA metabolism. Increasing BCAAs is not a therapeutic strategy for this condition.
- Excessive BCAA intake could potentially worsen metabolic imbalances without addressing the underlying enzymatic defect.
*Valine*
- **Valine** is another **branched-chain amino acid (BCAA)** with no specific role in managing PDC deficiency.
- Like isoleucine, valine supplementation does not address the **pyruvate dehydrogenase complex defect** and is not part of standard dietary management.
- BCAAs require careful monitoring in metabolic disorders and are not indicated for mitochondrial disorders like PDC deficiency.
*Leucine*
- **Leucine** is a **branched-chain amino acid (BCAA)** and potent activator of mTOR signaling for protein synthesis.
- Direct leucine supplementation is **not indicated for PDC deficiency** and does not address the metabolic block at the pyruvate dehydrogenase step.
- In disorders like **maple syrup urine disease (MSUD)**, BCAAs including leucine must be **restricted**, not supplemented.
*Methionine*
- **Methionine** is a sulfur-containing amino acid important for **methylation reactions** through S-adenosylmethionine (SAM) synthesis.
- There is **no established role** for methionine supplementation in **pyruvate dehydrogenase complex deficiency** or mitochondrial disorders presenting with lactic acidosis.
- Methionine metabolism is not directly related to the pathophysiology of PDC deficiency.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 6: A 7-month-old boy is brought to the pediatrician for a change in his behavior. The patient has been exclusively breastfeeding up until this point and has been meeting his developmental milestones. He is in the 90th percentile for weight and 89th percentile for height. Two weeks ago, his parents began introducing weaning foods including fruit purees and baby formula. This past week, the patient has been increasingly lethargic, vomiting, and has been refusing to eat. The patient's parents state that he had an episode this morning where he was not responsive and was moving his extremities abnormally followed by a period of somnolence. The patient's past medical history is notable for shoulder dystocia and poorly managed maternal diabetes during the pregnancy. His temperature is 99.5°F (37.5°C), blood pressure is 60/30 mmHg, pulse is 120/min, respirations are 17/min, and oxygen saturation is 98% on room air. On physical exam, you note a lethargic infant with a distinctive sweet, fruity smell to his breath. Which of the following is most likely deficient in this patient?
- A. Branched chain alpha-ketoacid dehydrogenase (Correct Answer)
- B. Galactose-1-phosphate uridyltransferase
- C. Aldolase B
- D. Glucose-6-phosphatase
- E. Ornithine transcarbamolase
Disorders of branched-chain amino acids (MSUD) Explanation: ***Branched chain alpha-ketoacid dehydrogenase***
- This patient's presentation is classic for **maple syrup urine disease (MSUD)**, caused by deficiency of branched chain alpha-ketoacid dehydrogenase complex.
- The **distinctive sweet, fruity smell to the breath** (and urine) is pathognomonic for MSUD, resulting from accumulation of branched chain amino acids (leucine, isoleucine, valine) and their ketoacid metabolites.
- Symptoms typically manifest upon introduction of **increased protein load** (baby formula), presenting with **lethargy, vomiting, poor feeding, seizures, and encephalopathy** due to neurotoxicity from elevated leucine and other metabolites.
- The timing (introduced weaning foods including formula) and clinical picture of acute metabolic crisis with characteristic odor make this the most likely diagnosis.
*Ornithine transcarbamylase*
- OTC deficiency causes **hyperammonemic crisis** with similar neurological symptoms (lethargy, vomiting, seizures) triggered by protein intake.
- However, hyperammonemia typically produces a **musty or ammonia-like odor**, NOT the sweet, fruity smell described in this case.
- While the clinical timing fits, the **characteristic breath odor is inconsistent** with urea cycle disorders.
*Galactose-1-phosphate uridyltransferase*
- Deficiency causes **classic galactosemia**, presenting with **vomiting, lethargy, jaundice, hepatomegaly, and cataracts** after lactose exposure (milk/formula).
- The **sweet, fruity breath odor is NOT characteristic** of galactosemia.
- While formula introduction could trigger symptoms, the specific odor and predominant neurological presentation point away from this diagnosis.
*Aldolase B*
- **Hereditary fructose intolerance** manifests upon fructose exposure (fruit purees) with **vomiting, hypoglycemia, jaundice, hepatomegaly, and renal dysfunction**.
- The patient did consume fruit purees, but the **sweet, fruity breath odor is NOT a feature** of fructose intolerance.
- The severe acute encephalopathy and characteristic odor make MSUD more likely.
*Glucose-6-phosphatase*
- **Von Gierke disease (Type I GSD)** presents with **severe fasting hypoglycemia, lactic acidosis, hepatomegaly, and hyperlipidemia**.
- The **sweet, fruity odor is NOT characteristic**, and symptoms are primarily related to fasting/glucose homeostasis rather than acute protein-induced metabolic crisis.
- The clinical picture does not fit a glycogen storage disorder.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 7: An 8-day-old boy is brought to the physician by his mother because of vomiting and poor feeding. The pregnancy was uncomplicated, and he was born at full term. He appears pale and lethargic. Physical examination shows diffusely increased muscle tone. His urine is noted to have a sweet odor. This patient's symptoms are most likely caused by the accumulation of which of the following?
- A. Phenylalanine
- B. Homogentisic acid
- C. Isoleucine (Correct Answer)
- D. Homocysteine
- E. Phytanic acid
Disorders of branched-chain amino acids (MSUD) Explanation: ***Isoleucine***
- The combination of **vomiting**, poor feeding, lethargy, **increased muscle tone**, and a **sweet-smelling urine** (often described as maple syrup odor) in a neonate strongly points to **Maple Syrup Urine Disease (MSUD)**.
- MSUD is caused by a defect in the **branched-chain alpha-keto acid dehydrogenase complex**, leading to the accumulation of branched-chain amino acids (leucine, isoleucine, and valine) and their corresponding alpha-keto acids.
*Phenylalanine*
- Accumulation of **phenylalanine** is characteristic of **Phenylketonuria (PKU)**, which typically presents with intellectual disability, seizures, and an eczematous rash if untreated, but not a maple syrup odor in urine or acute neonatal crisis.
- The urine odor in PKU is often described as **mousy** or musty, distinctly different from a sweet or maple syrup odor.
*Homogentisic acid*
- Accumulation of **homogentisic acid** is seen in **Alkaptonuria**, an inborn error of metabolism that primarily causes dark urine upon standing (due to oxidation of homogentisic acid), ochronosis (blue-black pigmentation of cartilage and connective tissue later in life), and arthritis.
- It does not present with acute neonatal symptoms such as vomiting, lethargy, or a sweet urine odor.
*Homocysteine*
- Elevated levels of **homocysteine** are found in **Homocystinuria**, which can lead to intellectual disability, developmental delay, dislocation of the ocular lens (ectopia lentis), Marfanoid habitus, and thromboembolic events.
- It does not typically present in the neonatal period with a sweet urine odor or acute neurological symptoms like increased muscle tone.
*Phytanic acid*
- Accumulation of **phytanic acid** is characteristic of **Refsum disease**, a rare peroxisomal disorder that causes progressive neurological symptoms such as retinitis pigmentosa, peripheral neuropathy, ataxia, and deafness in childhood or adulthood.
- It does not present in the neonatal period with the described acute symptoms or unique urine odor.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 8: A 7-year-old boy is brought to the emergency department because of sudden-onset abdominal pain that began 1 hour ago. Three days ago, he was diagnosed with a urinary tract infection and was treated with nitrofurantoin. There is no personal history of serious illness. His parents emigrated from Kenya before he was born. Examination shows diffuse abdominal tenderness, mild splenomegaly, and scleral icterus. Laboratory studies show:
Hemoglobin 9.8 g/dL
Mean corpuscular volume 88 μm3
Reticulocyte count 3.1%
Serum
Bilirubin
Total 3.8 mg/dL
Direct 0.6 mg/dL
Haptoglobin 16 mg/dL (N=41–165 mg/dL)
Lactate dehydrogenase 179 U/L
Which of the following is the most likely underlying cause of this patient's symptoms?
- A. Defective red blood cell membrane proteins
- B. Lead poisoning
- C. Defect in orotic acid metabolism
- D. Absent hemoglobin beta chain
- E. Enzyme deficiency in red blood cells (Correct Answer)
Disorders of branched-chain amino acids (MSUD) Explanation: ***Enzyme deficiency in red blood cells***
- The patient's symptoms (abdominal pain, scleral icterus, mild splenomegaly, anemia, elevated reticulocyte count, increased unconjugated bilirubin, low haptoglobin, and elevated LDH) are consistent with **hemolytic anemia**. The recent use of **nitrofurantoin**, an oxidative stressor, in a patient of African descent, strongly suggests a diagnosis of **Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency**.
- G6PD deficiency is an **X-linked recessive** inherited enzyme defect causing red blood cells to be susceptible to oxidative damage, leading to hemolysis when exposed to certain drugs (like nitrofurantoin) or infections.
*Defective red blood cell membrane proteins*
- This describes conditions like **hereditary spherocytosis** or **hereditary elliptocytosis**. While these cause hemolytic anemia, the acute onset triggered by a drug (nitrofurantoin) is less typical.
- Hereditary spherocytosis is characterized by **microspherocytes** on a peripheral smear and is usually diagnosed earlier in life or has a chronic course, often without an acute precipitating drug.
*Lead poisoning*
- Lead poisoning typically causes **microcytic anemia** with **basophilic stippling** and neurological symptoms, not the type of hemolytic anemia and jaundice described.
- It does not present as an acute hemolytic crisis triggered by an oxidative drug.
*Defect in orotic acid metabolism*
- This can lead to conditions like **hereditary orotic aciduria**, which presents with **megaloblastic anemia** (without B12 or folate deficiency) and developmental delay.
- It is not associated with acute hemolytic episodes triggered by oxidative drugs or the specific lab findings seen here.
*Absent hemoglobin beta chain*
- This refers to **beta-thalassemia major**, which causes **microcytic hypochromic anemia** that is typically chronic and presents early in childhood with severe anemia requiring regular transfusions.
- Beta-thalassemia does not present as an acute hemolytic crisis triggered by nitrofurantoin, and the MCV in this patient is normal (88 μm³), not microcytic.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 9: In a patient with maple syrup urine disease, all of the following amino acids should be restricted in diet except?
- A. Methionine (Correct Answer)
- B. Isoleucine
- C. Leucine
- D. Valine
Disorders of branched-chain amino acids (MSUD) Explanation: ***Methionine***
- **Maple syrup urine disease (MSUD)** is a disorder affecting the metabolism of **branched-chain amino acids (BCAAs)**: leucine, isoleucine, and valine.
- Therefore, methionine, which is not a BCAA, typically does not need to be restricted and is, in fact, an **essential amino acid** crucial for protein synthesis.
*Isoleucine*
- **Isoleucine** is a branched-chain amino acid (BCAA) whose metabolism is impaired in MSUD due to a deficiency in **branched-chain alpha-keto acid dehydrogenase complex**.
- Accumulation of isoleucine and its corresponding alpha-keto acid is toxic and must be **restricted in the diet**.
*Leucine*
- **Leucine** is another branched-chain amino acid (BCAA) that cannot be properly metabolized in MSUD.
- High levels of leucine and its metabolites are particularly **neurotoxic** and contribute to the characteristic neurological symptoms, necessitating strict dietary restriction.
*Valine*
- **Valine** is the third branched-chain amino acid (BCAA) whose breakdown is defective in MSUD.
- Dietary restriction of valine is essential to prevent its accumulation, which can lead to metabolic crises and **developmental delays**.
Disorders of branched-chain amino acids (MSUD) US Medical PG Question 10: An investigator is studying the activity level of several different enzymes in human subjects from various demographic groups. An elevated level of activity of phosphoribosyl pyrophosphate synthetase is found in one of the study subjects. This patient is most likely to have which of the following conditions?
- A. Phenylketonuria
- B. Homocystinuria
- C. Gout (Correct Answer)
- D. Alkaptonuria
- E. Maple syrup urine disease
Disorders of branched-chain amino acids (MSUD) Explanation: ***Gout***
- **Elevated phosphoribosyl pyrophosphate (PRPP) synthetase activity** leads to increased production of PRPP, a precursor for **purine biosynthesis**.
- Increased purine synthesis results in overproduction of **uric acid**, which can precipitate as monosodium urate crystals in joints, causing **gout**.
*Phenylketonuria*
- Caused by a deficiency in **phenylalanine hydroxylase**, leading to an accumulation of **phenylalanine**.
- Not directly related to increased PRPP synthetase activity or purine metabolism.
*Homocystinuria*
- Primarily due to a deficiency in **cystathionine beta-synthase**, leading to elevated levels of **homocysteine**.
- This condition involves methionine metabolism, not purine metabolism or PRPP synthetase.
*Alkaptonuria*
- Results from a deficiency in **homogentisate 1,2-dioxygenase**, causing the accumulation of **homogentisic acid**.
- It is an inborn error of tyrosine metabolism and is unrelated to PRPP synthetase activity.
*Maple syrup urine disease*
- Caused by a deficiency in the **branched-chain alpha-keto acid dehydrogenase complex**, leading to accumulation of **leucine, isoleucine, and valine**.
- This condition affects branched-chain amino acid metabolism, not purine metabolism.
More Disorders of branched-chain amino acids (MSUD) US Medical PG questions available in the OnCourse app. Practice MCQs, flashcards, and get detailed explanations.
