Single Gene Disorders Indian Medical PG Practice Questions and MCQs
Practice Indian Medical PG questions for Single Gene Disorders. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Single Gene Disorders Indian Medical PG Question 1: An infant presents with vomiting after feeding. Benedict's test was positive for a non-glucose reducing substance. What is the most likely diagnosis?
- A. Galactosemia due to GAL-1-P Uridyl Transferase enzyme deficiency (Correct Answer)
- B. Fructosuria due to Fructokinase deficiency
- C. Hereditary fructose intolerance due to Aldolase B deficiency
- D. Primary lactose intolerance
- E. Glycogen storage disease due to Glucose-6-phosphatase deficiency
Single Gene Disorders Explanation: ***Galactosemia due to GAL-1-P Uridyl Transferase enzyme deficiency***
- Vomiting after feeding in an infant, coupled with a **positive Benedict's test** for a **non-glucose reducing substance**, is highly indicative of galactosemia. The accumulation of **galactose-1-phosphate** and **galactitol** leads to toxicity and symptoms.
- This enzyme deficiency, causing **classic galactosemia**, prevents the proper metabolism of **galactose**, leading to its buildup.
*Fructosuria due to Fructokinase deficiency*
- This condition is a **benign metabolic disorder** with no significant clinical symptoms.
- While it would lead to fructose in the urine, the infant would not typically present with **vomiting after feeding**.
*Hereditary fructose intolerance due to Aldolase B deficiency*
- Symptoms usually appear after the introduction of **fructose-containing foods** into the diet, causing severe hypoglycemia and vomiting.
- The positive Benedict's test in this scenario would typically indicate a reducing substance in the urine, while fructose intolerance is characterized by **hypoglycemia** and metabolic crises upon fructose ingestion.
*Glycogen storage disease due to Glucose-6-phosphatase deficiency*
- This disorder primarily causes **hypoglycemia** and liver enlargement, not primarily vomiting after feeding due to a **non-glucose reducing substance**.
- Glucose-6-phosphatase deficiency (Von Gierke's disease) leads to an inability to release **glucose from glycogen** and causes severe hypoglycemia, often requiring frequent feeding.
*Primary lactose intolerance*
- While lactose intolerance can cause vomiting and gastrointestinal symptoms, it is **extremely rare in infants** (primary lactose intolerance is a late-onset condition).
- Lactose would be a reducing sugar, but the key differentiator is that **galactose** (from galactosemia) is the non-glucose reducing substance detected in this case, along with the typical **toxic presentation** in neonates.
Single Gene Disorders Indian Medical PG Question 2: Inheritance of Huntington's disease is
- A. Autosomal Dominant (Correct Answer)
- B. X-Linked Recessive
- C. Autosomal Recessive
- D. X-Linked Dominant
Single Gene Disorders Explanation: ***AD***
- Huntington's chorea is inherited in an **autosomal dominant** manner, meaning only one copy of the mutated gene is sufficient to cause the disorder [1].
- The disease typically manifests in mid-adulthood, with progressively worsening movement disorders and cognitive decline [1].
*XR*
- X-linked recessive disorders typically affect **males** and can be transmitted by carrier females; this is not the case for Huntington's chorea.
- The inheritance pattern does not align with the typical clinical presentation of Huntington's, which does not show a gender bias.
*XD*
- X-linked dominant disorders often affect both sexes, but their inheritance pattern does not describe Huntington's chorea.
- Symptoms and gene affected are clearly linked with **autosomal dominant** inheritance, not X-linked dominant.
*AR*
- Autosomal recessive conditions typically require two copies of the mutated gene, which is not applicable to Huntington's chorea.
- This pattern generally leads to earlier onset conditions and significantly different clinical presentations than those observed in Huntington's.
**References:**
[1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 149-150.
Single Gene Disorders Indian Medical PG Question 3: An affected male does not have affected children but an affected female always has affected children. Type of inheritance?
- A. Autosomal recessive
- B. Mitochondrial (Correct Answer)
- C. X linked recessive
- D. X linked dominant
Single Gene Disorders Explanation: ***Correct Option: Mitochondrial***
- This pattern describes **mitochondrial inheritance**, where all children of an **affected mother** inherit the condition because mitochondria are exclusively inherited from the ovum (maternal inheritance).
- An **affected father** cannot pass on the condition to his children, as sperm contribute only nuclear DNA and essentially no mitochondria.
- This is the **only inheritance pattern** where an affected male has no affected children while an affected female has all children affected.
*Incorrect Option: Autosomal recessive*
- This pattern would typically show affected individuals having unaffected parents (who are carriers) and both males and females being affected in equal proportions.
- It does not explain the complete absence of transmission from an affected father or universal transmission from an affected mother.
- An affected individual could have unaffected children if their partner is not a carrier.
*Incorrect Option: X linked recessive*
- In **X-linked recessive inheritance**, affected males cannot pass the trait to their sons, but all their daughters would be carriers (not affected).
- An affected mother would pass the trait to all her sons (affected) and make all her daughters carriers (not affected), which does not match the described pattern of all children being affected.
*Incorrect Option: X linked dominant*
- In **X-linked dominant inheritance**, an affected father passes the trait to all his daughters but none of his sons (contradicts "no affected children").
- An affected mother has a 50% chance of passing the trait to **each child**, which is inconsistent with all children of an affected female being affected.
Single Gene Disorders Indian Medical PG Question 4: Phenylketonuria is due to a deficiency of:
- A. Phenylalanine hydroxylase (PAH) (Correct Answer)
- B. Galactokinase
- C. Tyrosinase
- D. Phenylalanine
Single Gene Disorders Explanation: ***Phenylalanine hydroxylase (PAH)***
- **Phenylketonuria (PKU)** is an autosomal recessive disorder caused by a deficiency of the enzyme **phenylalanine hydroxylase (PAH)**.
- This enzyme is crucial for converting the amino acid **phenylalanine** to **tyrosine**.
*Phenylalanine*
- Phenylalanine is the **substrate** that accumulates in PKU due to the enzyme deficiency, not the deficiency itself.
- High levels of phenylalanine are **toxic** to the brain and lead to the clinical manifestations of PKU.
*Galactokinase*
- Deficiency of **galactokinase** is associated with **galactosemia type II**, a disorder of galactose metabolism.
- This condition is characterized by **cataracts** and typically does not involve the neurologic symptoms seen in PKU.
*Tyrosinase*
- **Tyrosinase** deficiency is the primary cause of **oculocutaneous albinism type 1**, affecting melanin synthesis.
- It results in hypopigmentation of the skin, hair, and eyes, which is unrelated to PKU.
Single Gene Disorders Indian Medical PG Question 5: 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
Single Gene Disorders 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**.
Single Gene Disorders Indian Medical PG Question 6: Which of the following statements about the enzyme aldolase B is false?
- A. The enzyme cleaves fructose-1-phosphate into dihydroxyacetone phosphate and glyceraldehyde
- B. The enzyme involved catalyzes the conversion of fructose to fructose-1 phosphate (Correct Answer)
- C. The enzyme is involved in fructose metabolism
- D. The enzyme is found primarily in liver, kidney, and intestine
Single Gene Disorders Explanation: ***The enzyme involved catalyzes the conversion of fructose to fructose-1 phosphate***
- This statement is **false** because the enzyme that catalyzes the conversion of **fructose to fructose-1-phosphate** is **fructokinase**, not aldolase B.
- Aldolase B acts further down the pathway, cleaving fructose-1-phosphate.
*The enzyme is involved in fructose metabolism*
- Aldolase B is indeed a crucial enzyme in **fructose metabolism**, specifically in the breakdown of **fructose-1-phosphate**.
- Its role is to convert fructose-1-phosphate into usable glycolytic intermediates.
*The enzyme cleaves fructose-1-phosphate into dihydroxyacetone phosphate and glyceraldehyde*
- This statement accurately describes the primary catalytic action of **aldolase B**, which is the cleavage of **fructose-1-phosphate**.
- This cleavage yields **dihydroxyacetone phosphate (DHAP)** and **glyceraldehyde**, which can then enter glycolysis.
*The enzyme is found primarily in liver, kidney, and intestine*
- Aldolase B is predominantly expressed in the **liver**, **kidney**, and **small intestine**, organs that are key sites for processing dietary fructose.
- This distribution reflects its critical role in fructose metabolism in these tissues.
Single Gene Disorders Indian Medical PG Question 7: In which of the following inheritance patterns is father-to-son transmission not observed?
- A. Autosomal dominant inheritance
- B. Autosomal recessive inheritance
- C. Multifactorial inheritance
- D. X-linked recessive inheritance (Correct Answer)
Single Gene Disorders Explanation: ***X-linked recessive inheritance***
- In X-linked inheritance, females have two X chromosomes (XX) and males have one X and one Y chromosome (XY). A father always passes his **Y chromosome** to his son.
- He passes his **X chromosome only to his daughters**. Therefore, a father cannot pass an X-linked trait directly to his son.
*Autosomal dominant inheritance*
- In autosomal dominant inheritance, a disease allele is located on a **non-sex chromosome (autosome)**.
- Both males and females can be affected, and **father-to-son transmission is possible** if the father carries the dominant allele on an autosome.
*Autosomal recessive inheritance*
- This inheritance pattern also involves genes on **autosomes**.
- A father can transmit a recessive allele to his son, though the son would only express the trait if he also inherits a recessive allele from his mother. **Father-to-son transmission of the allele is possible**.
*Multifactorial inheritance*
- This pattern involves the interaction of **multiple genes** and **environmental factors**.
- As some of these genes are on autosomes, and environmental factors are independent of sex chromosomes, **father-to-son transmission is observed** for the genetic components.
Single Gene Disorders Indian Medical PG Question 8: Which one of the following is an autosomal dominant disorder?
- A. Cystic fibrosis
- B. Hereditary spherocytosis (Correct Answer)
- C. Sickle cell anemia
- D. G-6PD deficiency
Single Gene Disorders Explanation: ***Hereditary spherocytosis***
- It is characterized by **autosomal dominant inheritance** [1], leading to the destruction of red blood cells.
- Mutations in proteins that maintain the **red blood cell membrane** integrity result in spherocyte formation [1].
*Cystic fibrosis*
- This condition follows a **autosomal recessive inheritance pattern**, requiring two copies of the mutated gene for disease manifestation.
- It is caused by mutations in the **CFTR gene**, affecting chloride transport and leading to thick secretions.
*G-6PD deficiency*
- This disorder is inherited in an **X-linked recessive manner** [2], primarily affecting males and transmitted through carrier females.
- Characterized by **hemolytic anemia** triggered by certain medications or infections, it does not follow dominant inheritance [2].
*Sickle cell anemia*
- Sickle cell anemia is also an **autosomal recessive disorder** [3], meaning affected individuals must inherit two copies of the sickle cell gene.
- It results in a mutation in the **HBB gene**, leading to the production of abnormal hemoglobin (HbS) [3].
Single Gene Disorders Indian Medical PG Question 9: A 6-year-old presents with developmental delay, musty body odor, and fair skin. Lab tests show high phenylalanine levels. What is the most appropriate management?
- A. Low-phenylalanine diet (Correct Answer)
- B. Avoidance of ascorbic acid
- C. Vitamin D supplementation
- D. High-protein diet
- E. Tetrahydrobiopterin (BH4) supplementation
Single Gene Disorders Explanation: ***Low-phenylalanine diet***
- The patient's symptoms (developmental delay, musty body odor, fair skin) and high **phenylalanine levels** are classic for **phenylketonuria (PKU)**.
- Management primarily involves a strict **low-phenylalanine diet** to prevent further neurological damage.
- This is the **cornerstone of PKU management** and must be initiated as early as possible.
*Tetrahydrobiopterin (BH4) supplementation*
- While **BH4 (sapropterin)** can be beneficial in some patients with **BH4-responsive PKU** (a subset of PKU cases), it is not first-line management.
- BH4 testing is performed after diagnosis, but dietary restriction remains the primary treatment.
- Not all PKU patients respond to BH4, and it's used as an adjunct, not a replacement for dietary management.
*Avoidance of ascorbic acid*
- **Ascorbic acid** (vitamin C) is generally not contraindicated in PKU and does not impact phenylalanine metabolism.
- This intervention is not relevant to the management of PKU.
*Vitamin D supplementation*
- While vitamin D supplementation might be necessary for general health, especially in children with restricted diets, it is not the primary treatment for **phenylketonuria (PKU)**.
- It does not directly address the elevated phenylalanine levels.
*High-protein diet*
- A **high-protein diet** would exacerbate the condition, as proteins are a major source of phenylalanine.
- This would lead to even higher phenylalanine levels and worsen the symptoms of PKU.
Single Gene Disorders Indian Medical PG Question 10: A neonate was brought to the hospital with chief complaints of poor feeding, vomiting, acidosis, and cataract. Benedict's test on urine was positive, but urinary glucose was negative. What is the defective enzyme in the above-mentioned disorder?
- A. Galactose 1-phosphate uridyl transferase (Correct Answer)
- B. Fructokinase
- C. Lactase
- D. Sucrase
- E. Aldolase B
Single Gene Disorders Explanation: ***Galactose 1-phosphate uridyl transferase***
- This enzyme deficiency leads to **classic galactosemia**, characterized by the accumulation of **galactose-1-phosphate**, which is toxic.
- Clinical features like **poor feeding, vomiting, acidosis, and cataracts** are typical, and a positive **Benedict's test** (detecting reducing sugars like galactose) with negative urinary glucose confirms the presence of another reducing sugar.
*Fructokinase*
- Deficiency of fructokinase causes **essential fructosuria**, a benign condition where **fructose** accumulates in the urine.
- Unlike classic galactosemia, it does not present with severe symptoms like **acidosis** or **cataracts**.
*Aldolase B*
- **Aldolase B deficiency** causes hereditary fructose intolerance, presenting with **vomiting, hypoglycemia, and hepatomegaly** after fructose ingestion.
- It does not cause **cataracts**, and Benedict's test would detect fructose, but the clinical context (symptoms with fructose/sucrose intake) differs from galactosemia.
*Lactase*
- **Lactase deficiency** (lactose intolerance) results in gastrointestinal symptoms such as **bloating, diarrhea, and abdominal pain** upon lactose consumption.
- It does not typically cause **acidosis, cataracts**, or a positive Benedict's test in urine unless secondary bacterial fermentation leads to other reducing substances.
*Sucrase*
- **Sucrase-isomaltase deficiency** leads to the malabsorption of sucrose, causing symptoms similar to lactose intolerance like **diarrhea and abdominal cramping**.
- It does not result in the systemic, severe metabolic derangements or signs like **cataracts** seen in classic galactosemia.
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