Disorders of Fructose and Galactose Metabolism — MCQs
Which amino acids accumulate in maple syrup urine disease?
History of dislike for sweet food items is typically present in:
Which enzyme is deficient in Galactosemia?
An 8-month-old infant is brought in with poor feeding, lethargy, hypotonia, and hepatomegaly. Labs reveal hypoglycemia and metabolic acidosis. Which condition is most likely?
A cataract formation in both eyes was discovered in a 1-year-old child during a routine well-child visit, with blood tests showing elevated galactose and galactitol levels. To determine which enzyme might be defective in the child, which intracellular metabolite should be measured?
Which carbohydrate is primarily metabolized by Aldolase-B?
What are the immediate metabolic products formed during the conversion of Fructose 1,6-bisphosphate to two molecules of pyruvate?
Fructose intolerance is due to deficiency of which enzyme?
Most Common enzyme deficient in galactosemics:
Congenital lactic acidosis is primarily due to a defect in which enzyme?
Disorders of Fructose and Galactose Metabolism Indian Medical PG Practice Questions and MCQs
Question 1: Which amino acids accumulate in maple syrup urine disease?
- A. Valine
- B. Leucine
- C. Isoleucine
- D. All branched-chain amino acids (Correct Answer)
Explanation: ***All branched-chain amino acids*** - Maple syrup urine disease (MSUD) is characterized by a deficiency in the **branched-chain alpha-keto acid dehydrogenase complex**, which is responsible for the breakdown of branched-chain amino acids (BCAAs). - This deficiency leads to the accumulation of **leucine, isoleucine, and valine**, along with their corresponding alpha-keto acids, in the blood and urine. - The distinctive **maple syrup odor** in the urine is caused by the accumulation of branched-chain keto acids derived from all three BCAAs. *Leucine* - While leucine is one of the BCAAs that accumulates in MSUD, it is not the *only* amino acid involved. - The accumulation of **leucine** is particularly associated with the severe neurological symptoms seen in MSUD, as it is the most neurotoxic of the three BCAAs. *Valine* - Valine is another BCAA that accumulates due to the metabolic block in MSUD. - However, the disease involves the accumulation of all three BCAAs, not just valine in isolation. *Isoleucine* - Isoleucine is the third BCAA that accumulates in MSUD due to the defective enzyme. - Like leucine and valine, isoleucine and its corresponding keto acid accumulate in blood and urine when the branched-chain alpha-keto acid dehydrogenase complex is deficient.
Question 2: History of dislike for sweet food items is typically present in:
- A. Glycogen storage disease
- B. Diabetes mellitus
- C. Galactosemia
- D. Hereditary fructose intolerance (Correct Answer)
Explanation: ***Hereditary fructose intolerance*** - Patients with hereditary fructose intolerance develop severe symptoms like **nausea, vomiting, abdominal pain, and hypoglycemia** after ingesting fructose, leading to an aversive response and **dislike for sweet food items**. - This aversion is a protective mechanism, as avoiding fructose-containing foods (including many sweets) prevents the accumulation of toxic metabolites due to a deficiency in **hepatic aldolase B**. *Glycogen storage disease* - While glycogen storage diseases can cause hypoglycemia, they typically do not lead to a specific **aversion to sweet foods**. - The primary defect is in **glycogen synthesis or breakdown**, leading to symptoms like hepatomegaly, muscle weakness, and exercise intolerance. *Diabetes mellitus* - Patients with diabetes mellitus often have a **craving for sweet foods** due to uncontrolled blood glucose levels and insulin resistance, rather than a dislike. - The condition is characterized by **hyperglycemia** and may involve polydipsia, polyuria, and polyphagia. *Galactosemia* - Galactosemia involves an inability to metabolize galactose, leading to symptoms such as **vomiting, lethargy, and jaundice** upon milk ingestion [1]. - While patients will avoid milk, their aversion is not generally to all sweet foods, as sweet foods do not always contain galactose [1].
Question 3: Which enzyme is deficient in Galactosemia?
- A. Hexosaminidase B
- B. Hexosaminidase A
- C. Galactose 1-phosphate uridyltransferase (Correct Answer)
- D. Glucocerebrosidase
Explanation: ***Galactose 1-phosphate uridyltransferase*** - **Classical galactosemia** (Type I) is caused by a deficiency in this enzyme, which converts **galactose-1-phosphate** and UDP-glucose into UDP-galactose and glucose-1-phosphate. - This deficiency leads to the accumulation of toxic galactose metabolites, such as **galactitol** and galactose-1-phosphate. *Hexosaminidase B* - Deficiency of this enzyme is seen in **Sandhoff disease**, a lysosomal storage disorder, which leads to the accumulation of **GM2 gangliosides** in neurons. - This enzyme is less commonly associated with the primary defect in **Tay-Sachs disease**, which is predominantly due to hexosaminidase A deficiency. *Hexosaminidase A* - A deficiency in **hexosaminidase A** causes **Tay-Sachs disease**, another lysosomal storage disorder, leading to the accumulation of **GM2 gangliosides** primarily in nerve cells. - This enzyme is not involved in the metabolism of galactose. *Glucocerebrosidase* - A deficiency in **glucocerebrosidase** causes **Gaucher disease**, which leads to the accumulation of **glucocerebroside** in macrophages and other cells. - This enzyme is not involved in the metabolic pathway of galactose.
Question 4: An 8-month-old infant is brought in with poor feeding, lethargy, hypotonia, and hepatomegaly. Labs reveal hypoglycemia and metabolic acidosis. Which condition is most likely?
- A. Hereditary fructose intolerance
- B. Galactosemia
- C. Pompe disease
- D. Von Gierke disease (Correct Answer)
- E. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
Explanation: ***Von Gierke disease*** - **Type I glycogen storage disease** (GSD I) typically presents in infancy with **hypoglycemia** (due to impaired glucose release from glycogen), **hepatomegaly** (due to glycogen accumulation), and **lactic acidosis**. - Other common findings include **hyperlipidemia** and **hyperuricemia**, while **hypotonia** and **poor feeding** are generalized symptoms stemming from metabolic derangements. *Hereditary fructose intolerance* - This condition presents when **fructose** is introduced into the diet, typically after 4-6 months of age, with symptoms like **nausea, vomiting, abdominal pain**, and **hepatomegaly**. - While it can cause **hypoglycemia** and **metabolic acidosis**, the profound **hypotonia** and general metabolic collapse described in an 8-month-old on a typical diet makes GSD I more likely initially. *Galactosemia* - Symptoms usually appear within days or weeks of birth upon the initiation of **milk feeding**, including **vomiting, lethargy, poor feeding, jaundice, hepatomegaly**, and **cataracts**. - While it causes **hypoglycemia** and can lead to acidosis and hypotonia, the age of presentation and lack of specific mention of jaundice or cataracts makes it a less precise fit. *Pompe disease* - Also known as **glycogen storage disease type II**, it is characterized by the accumulation of glycogen in **lysosomes**, primarily affecting muscles. - The infantile form presents with severe **cardiomyopathy**, **muscle weakness**, and **hypotonia**, but **hypoglycemia** and **hepatomegaly** are not its primary or most prominent features. *Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency* - A **fatty acid oxidation disorder** that presents with episodic **hypoglycemia** (particularly during fasting or illness), **lethargy**, and **hepatomegaly**. - Key distinguishing features include **hypoketotic hypoglycemia** and elevated **dicarboxylic acids** on urine organic acids, but the **lactic acidosis** and overall metabolic profile are more consistent with GSD I.
Question 5: A cataract formation in both eyes was discovered in a 1-year-old child during a routine well-child visit, with blood tests showing elevated galactose and galactitol levels. To determine which enzyme might be defective in the child, which intracellular metabolite should be measured?
- A. Galactose
- B. Fructose
- C. Glucose
- D. Galactose-1-phosphate (Correct Answer)
Explanation: ***Galactose-1-phosphate*** - An elevation of **galactose-1-phosphate** in a patient with cataracts and elevated galactose and galactitol levels points to a deficiency in **galactose-1-phosphate uridyltransferase (GALT)**, indicating **classic galactosemia**. - The accumulation of **galactose-1-phosphate** is toxic and underlies the severe symptoms of classic galactosemia, including cataracts, liver damage, and intellectual disability. - Measuring this metabolite specifically identifies GALT deficiency and distinguishes it from other enzyme defects in galactose metabolism. *Galactose* - Elevated **galactose** is observed in **galactosemia**, but measuring galactose itself doesn't differentiate between the different enzyme deficiencies (e.g., GALT vs. GALK deficiency). - While elevated, it's the downstream metabolites like **galactose-1-phosphate** that are more specific for diagnosing the enzyme defect in classic galactosemia. *Fructose* - **Fructose** metabolism is distinct from galactose metabolism, and its levels would not be directly affected by defects in galactose-metabolizing enzymes. - Elevated fructose would suggest a different metabolic disorder, such as **hereditary fructose intolerance**, which has different clinical presentations. *Glucose* - **Glucose** levels are not specific for diagnosing enzyme defects in galactose metabolism. - While hypoglycemia can occur in severe galactosemia, measuring glucose doesn't identify which specific enzyme is deficient and is not the primary diagnostic metabolite.
Question 6: Which carbohydrate is primarily metabolized by Aldolase-B?
- A. Galactose
- B. Fructose (Correct Answer)
- C. Sucrose
- D. None of the options
Explanation: ***Fructose*** - **Aldolase B** is a key enzyme in the liver responsible for the metabolism of **fructose**, specifically cleaving **fructose-1-phosphate** into **dihydroxyacetone phosphate** and **glyceraldehyde**. - A deficiency in **Aldolase B** leads to **hereditary fructose intolerance**, causing an accumulation of **fructose-1-phosphate** after fructose ingestion. *Galactose* - **Galactose** is primarily metabolized by enzymes in the **Leloir pathway**, including **galactokinase** and **galactose-1-phosphate uridylyltransferase**. - **Aldolase B** plays no significant role in the metabolism of galactose. *Sucrose* - **Sucrose** is a disaccharide composed of **glucose** and **fructose**. - It is first broken down by **sucrase** in the small intestine into its constituent monosaccharides before they are metabolized further. *None of the options* - This option is incorrect because **fructose** is indeed a carbohydrate primarily metabolized by Aldolase-B. - The enzyme's specific role in fructose metabolism is well-established.
Question 7: What are the immediate metabolic products formed during the conversion of Fructose 1,6-bisphosphate to two molecules of pyruvate?
- A. Glyceraldehyde-3-phosphate and 1,3-bisphosphoglycerate
- B. Dihydroxyacetone phosphate and 1,3 bisphosphoglycerate
- C. Glyceraldehyde-3-phosphate and dihydroxy-acetone phosphate (Correct Answer)
- D. 3-phosphoglycerate and 1,3 bisphosphoglycerate
Explanation: ***Glyceraldehyde-3-phosphate and dihydroxy-acetone phosphate*** - Fructose-1,6-bisphosphate is cleaved by the enzyme **aldolase** into two 3-carbon isomers: **dihydroxyacetone phosphate (DHAP)** and **glyceraldehyde-3-phosphate (GAP)**. - This reaction is a key step in **glycolysis**, occurring after the phosphorylation of fructose-6-phosphate. *Glyceraldehyde-3-phosphate and 1,3-bisphosphoglycerate* - **1,3-bisphosphoglycerate** is formed later in glycolysis from glyceraldehyde-3-phosphate, catalyzed by **glyceraldehyde-3-phosphate dehydrogenase**, not directly from Fructose-1,6-bisphosphate cleavage. - The initial products of Fructose-1,6-bisphosphate cleavage are two distinct three-carbon compounds, not one three-carbon compound and one already modified intermediate. *Dihydroxyacetone phosphate and 1,3 bisphosphoglycerate* - Similar to the above, **1,3-bisphosphoglycerate** is a product of an oxidation and phosphorylation step following the initial cleavage, not an immediate product of Fructose-1,6-bisphosphate breakdown. - The enzyme **triose phosphate isomerase** quickly interconverts dihydroxyacetone phosphate to glyceraldehyde-3-phosphate, ensuring that both can proceed through the subsequent steps of glycolysis. *3-phosphoglycerate and 1,3 bisphosphoglycerate* - **3-phosphoglycerate** is formed from 1,3-bisphosphoglycerate by the enzyme **phosphoglycerate kinase**, a later step in glycolysis where ATP is generated. - Neither of these molecules are the direct products of the enzymatic cleavage of Fructose-1,6-bisphosphate by aldolase.
Question 8: Fructose intolerance is due to deficiency of which enzyme?
- A. Aldolase B (Correct Answer)
- B. Aldolase A
- C. Fructokinase
- D. Triokinase
Explanation: ***Aldolase B*** - **Hereditary fructose intolerance** is a genetic disorder caused by a deficiency in the enzyme **aldolase B**. - This deficiency leads to an accumulation of **fructose-1-phosphate** in the liver, kidneys, and small intestine, causing **hypoglycemia**, **vomiting**, and **liver damage** upon exposure to fructose. *Fructokinase* - A deficiency in **fructokinase** causes **essential fructosuria**, a benign metabolic disorder. - This condition is asymptomatic because **fructose** simply accumulates in the blood and urine without causing significant clinical problems. *Triokinase* - **Triokinase**, also known as **glycerol kinase**, is involved in glycerol metabolism, converting glycerol to **glycerol-3-phosphate**. - Its deficiency is not directly linked to fructose intolerance and typically presents with **hyperglycerolemia**. *Aldolase A* - **Aldolase A** is one of the three aldolase isoenzymes (A, B, and C) and is primarily involved in **glycolysis**, specifically in the breakdown of **fructose-1,6-bisphosphate**. - A deficiency in aldolase A can lead to **hemolytic anemia** and **myopathy**, not directly fructose intolerance.
Question 9: Most Common enzyme deficient in galactosemics:
- A. Galactosidase
- B. UDP galactose epimerase
- C. Galactokinase
- D. Galactose-1-phosphate uridyl transferase/GALT (Correct Answer)
Explanation: ***Galactose-1-phosphate uridyl transferase/GALT*** - **GALT deficiency** is the most common cause of **classic galactosemia** (Type I), a severe inherited metabolic disorder. - This enzyme is crucial for converting **galactose-1-phosphate** to **glucose-1-phosphate** in the main pathway of galactose metabolism. - Accounts for approximately **95%** of all galactosemia cases. *Galactosidase* - **Galactosidase** enzymes are involved in the hydrolysis of galactose-containing oligosaccharides or glycoconjugates but are not the primary enzymes deficient in classic galactosemia. - This enzyme is not part of the Leloir pathway of galactose metabolism, which is the pathway affected in galactosemia. *UDP galactose epimerase* - Deficiency of **UDP galactose epimerase** (GALE) causes a milder form of galactosemia (Type III), but it is much less common than GALT deficiency. - GALE is involved in the interconversion of UDP-galactose and UDP-glucose. - This is the rarest form of galactosemia. *Galactokinase* - **Galactokinase deficiency** (GALK) causes a different, milder form of galactosemia (Type II), characterized by **cataracts** as the primary symptom. - It prevents the initial phosphorylation of galactose to galactose-1-phosphate. - This accounts for less than 5% of galactosemia cases.
Question 10: Congenital lactic acidosis is primarily due to a defect in which enzyme?
- A. Branched chain alpha-ketoacid dehydrogenase
- B. Isocitrate dehydrogenase (IDH)
- C. Transketolase
- D. Pyruvate dehydrogenase (Correct Answer)
Explanation: ***Pyruvate dehydrogenase*** - A defect in **pyruvate dehydrogenase (PDH)** complex prevents the conversion of **pyruvate to acetyl-CoA**, shunting pyruvate to **lactate production**. - This leads to an accumulation of **lactic acid** in the body, causing **congenital lactic acidosis**. *Branched chain alpha-ketoacid dehydrogenase* - A defect in **branched-chain alpha-ketoacid dehydrogenase** is responsible for **Maple Syrup Urine Disease**, not congenital lactic acidosis. - This enzyme is crucial for the metabolism of **branched-chain amino acids** (leucine, isoleucine, and valine). *Isocitrate dehydrogenase (IDH)* - **Isocitrate dehydrogenase (IDH)** is an enzyme in the **Krebs cycle** that converts isocitrate to alpha-ketoglutarate. - Defects or mutations in IDH enzymes are associated with certain **cancers**, but not primarily with congenital lactic acidosis. *Transketolase* - **Transketolase** is an enzyme involved in the **pentose phosphate pathway**, which generates NADPH and C5 sugars. - A deficiency in transketolase is associated with **Wernicke-Korsakoff syndrome** due to thiamine deficiency, not congenital lactic acidosis.
Want unlimited practice?
Get full access to all questions, explanations, and performance tracking.
Start For Free