Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology Indian Medical PG Practice Questions and MCQs

Question 701: Albinism is due to deficiency of the following enzyme?

A. Phenylalanine hydroxylase
B. Homogentisic acid oxidase
C. Tyrosinase (Correct Answer)
D. Decarboxylase

Explanation: ***Tyrosinase*** - **Albinism** is characterized by a lack of melanin production, which is primarily due to a defect in the enzyme **tyrosinase**. - **Tyrosinase** is crucial for converting **tyrosine** into **DOPA**, a key step in the biosynthesis of melanin. *Phenylalanine hydroxylase* - Deficiency of **phenylalanine hydroxylase** leads to **phenylketonuria (PKU)**, an inherited metabolic disorder. - This enzyme is responsible for converting **phenylalanine to tyrosine**, not directly involved in melanin synthesis. *Homogentisic acid oxidase* - A deficiency in **homogentisic acid oxidase** causes **alkaptonuria**, a rare metabolic disorder. - This enzyme is involved in the breakdown pathway of **tyrosine and phenylalanine**, causing homogentisic acid accumulation, which results in dark urine and ochronosis. *Decarboxylase* - The term "decarboxylase" refers to a general class of enzymes that remove a **carboxyl group** from a compound. - While decarboxylation reactions occur in many metabolic pathways, no single decarboxylase deficiency is directly responsible for **albinism**.

Question 702: Tuberous sclerosis caused by mutations in TSC2 gene encodes which of the following proteins?

A. Hamartin
B. Tuberin (Correct Answer)
C. Merlin
D. Ankyrin

Explanation: ***Tuberin*** - The **TSC2 gene** codes for the protein **tuberin**, which forms a complex with hamartin (encoded by TSC1). - This **tuberin-hamartin complex** functions as a tumor suppressor by negatively regulating the mTOR pathway. *Hamartin* - **Hamartin** is encoded by the **TSC1 gene**, not TSC2. - While it forms a complex with tuberin (TSC2 gene product), it is a distinct protein. *Merlin* - **Merlin** is a protein encoded by the **NF2 gene**, which is associated with **Neurofibromatosis type 2 (NF2)**, not tuberous sclerosis. - It plays a role in cell growth regulation and cell-cell adhesion. *Ankyrin* - **Ankyrin** proteins are a family of adapter proteins that link integral membrane proteins to the spectrin-actin cytoskeleton. - They are involved in many cellular processes but are **not directly encoded by the TSC2 gene** nor are they primarily associated with tuberous sclerosis.

Question 703: What is the underlying defect in Ataxia telangiectasia?

A. Double-strand DNA break repair (Correct Answer)
B. Nucleotide Excision Repair
C. Mismatch Repair
D. Base Excision Repair

Explanation: ***ds DNA break repair*** - Ataxia telangiectasia is primarily caused by a defect in the **ATM gene**, which plays a critical role in **double-strand DNA break repair** [1]. - Patients often present with **ataxia**, **telangiectasia**, and an increased risk of **cancers** due to impaired DNA repair mechanisms [1]. *Nucleotide Excision repair* - This pathway is responsible for repairing **DNA damage** caused by UV light and chemical exposure, which is not the defect in ataxia telangiectasia. - Disorders like **xeroderma pigmentosum** stem from defects in this pathway [1], not ataxia telangiectasia. *Mismatch repair* - Mismatch repair is important for correcting errors that occur during **DNA replication**, leading to conditions like **Lynch syndrome** when defective. - Ataxia telangiectasia is not associated with errors in this process, thus making it an incorrect option. *Base Excision Repair* - This repair mechanism handles small-scale DNA damage, especially from oxidative stress, which does not relate to ataxia telangiectasia pathology. - Conditions like **familial adenomatous polyposis** are associated with base excision repair defects, highlighting the difference. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 322-323.

Question 704: Refsum's disease is due to deficiency of which of the following enzyme?

A. Thiophorase
B. Succinate thiokinase
C. Phytanic alpha oxidase (Correct Answer)
D. Malonate dehydrogenase

Explanation: ***Phytanic alpha oxidase*** - **Refsum's disease** is an **autosomal recessive peroxisomal disorder** characterized by the accumulation of **phytanic acid**. - This accumulation occurs due to the deficiency of **phytanic acid alpha-oxidase**, an enzyme crucial for the **alpha-oxidation** of branched-chain fatty acids. *Malonate dehydrogenase* - This enzyme is involved in the metabolism of **malonate**, typically oxidizing it to **malonyl-CoA**. - Its deficiency is not associated with Refsum's disease or the accumulation of phytanic acid. *Thiophorase* - Also known as **succinyl-CoA:3-ketoacid CoA transferase**, thiophorase is involved in **ketone body metabolism**. - Its deficiency leads to **succinyl-CoA:3-ketoacid CoA transferase deficiency**, causing **ketoacidosis**, not Refsum's disease. *Succinate thiokinase* - Also known as **succinyl-CoA synthetase**, this enzyme plays a role in the **Krebs cycle**, converting **succinyl-CoA to succinate**. - Its deficiency is a rare metabolic disorder presenting with **encephalopathy and lactic acidosis**, unrelated to phytanic acid metabolism.

Question 705: Inheritance associated with fragile X syndrome is-

A. X-linked dominant (Correct Answer)
B. Autosomal dominant
C. Autosomal recessive
D. X-linked recessive

Explanation: ***X-linked dominant*** - Fragile X syndrome is caused by a **trinucleotide repeat expansion** (CGG) in the **FMR1 gene** located on the X chromosome. - The inheritance pattern is **X-linked dominant with reduced penetrance** and variable expressivity. - Males are typically more severely affected due to having only one X chromosome (hemizygous state). - **Importantly, carrier females are often affected** - approximately 50% show mild to moderate intellectual disability, anxiety, or social difficulties, which distinguishes it from X-linked recessive inheritance. - The condition shows **genetic anticipation** - repeat expansions increase in successive generations, particularly through maternal transmission. *X-linked recessive inheritance* - In true X-linked recessive disorders (like hemophilia A), carrier females are typically asymptomatic. - Fragile X syndrome does not fit this pattern because **carrier females frequently manifest symptoms**, making it dominant rather than recessive. - If it were recessive, heterozygous females would be unaffected carriers. *Autosomal dominant inheritance* - This pattern involves genes on autosomes (non-sex chromosomes) affecting males and females equally. - Fragile X syndrome is **X-linked**, not autosomal - the FMR1 gene is located on the X chromosome. - The sex-linked nature explains the higher prevalence and severity in males. *Autosomal recessive inheritance* - This pattern requires two copies of a mutated gene on autosomes, with both parents typically being carriers. - Fragile X syndrome is **X-linked**, not autosomal, and shows sex-specific inheritance patterns. - The pattern of inheritance through the X chromosome rules out any autosomal pattern.

Question 706: Trinucleotide sequence associated with spinocerebellar ataxia is?

A. CAG (Correct Answer)
B. CUG
C. GGC
D. CGG

Explanation: ***CAG*** - The **CAG trinucleotide repeat** is associated with **most forms of spinocerebellar ataxia (SCA)**, including SCA1, SCA2, SCA3 (Machado-Joseph disease), SCA6, SCA7, and SCA17. - An expansion of this repeat leads to an elongated **polyglutamine tract** in the affected protein, causing protein misfolding and neuronal dysfunction. - CAG is the **most common** trinucleotide repeat expansion associated with SCA. *CUG* - **CUG repeats** are primarily associated with **myotonic dystrophy type 1**. - While CUG expansions are found in **SCA8**, CAG repeats are far more commonly associated with the majority of spinocerebellar ataxias. - The expansion of CUG repeats in the **3' untranslated region** causes RNA-mediated toxicity. *GGC* - **GGC repeats** are not a common trinucleotide expansion associated with classic spinocerebellar ataxia. - While other repeat expansions exist in various genetic disorders, GGC is not the primary repeat linked to SCA. *CGG* - **CGG trinucleotide repeat** expansions are characteristic of **Fragile X syndrome**, a common cause of inherited intellectual disability. - This repeat expansion occurs in the FMR1 gene and is not the primary repeat associated with spinocerebellar ataxia.

Question 707: Acute intermittent porphyria is associated with which type of inheritance?

A. Autosomal dominant (Correct Answer)
B. Autosomal recessive
C. X-linked dominant
D. X-linked recessive

Explanation: ***Autosomal dominant*** - **Acute intermittent porphyria (AIP)** is inherited in an **autosomal dominant** pattern, meaning only one copy of the mutated gene (HMBS gene) is sufficient to cause the disorder. - This inheritance pattern leads to a 50% chance of passing the condition to each offspring from an affected parent. - **Important clinical feature:** AIP demonstrates **incomplete penetrance** (10-20%), meaning many individuals with the mutation never develop clinical symptoms, which is why family history may appear negative despite autosomal dominant inheritance. *Autosomal recessive* - **Autosomal recessive** disorders require two copies of the mutated gene (one from each parent) for the disease to manifest. - This pattern is characteristic of conditions like cystic fibrosis or sickle cell anemia, not acute intermittent porphyria. *X-linked dominant* - **X-linked dominant** inheritance involves a gene located on the X chromosome, where a single copy of the mutated gene is sufficient for disease expression in both males and females. - This pattern is typically seen in conditions such as fragile X syndrome or Rett syndrome, with distinct inheritance patterns differing from AIP. *X-linked recessive* - **X-linked recessive** disorders, such as hemophilia or Duchenne muscular dystrophy, primarily affect males as they only have one X chromosome. - Females are typically carriers but can be affected if they inherit two mutated X chromosomes, a pattern not seen in acute intermittent porphyria.

Question 708: Match the enzyme with the disease caused due to its deficiency: Enzymes: 1. Fumarylacetoacetate hydrolase 2. Tyrosine transaminase 3. Tyrosinase 4. Homogentisate oxidase Diseases: A. Tyrosinemia Type I B. Tyrosinemia Type II C. Albinism D. Alkaptonuria

A. 1 → A, 2 → B, 3 → C, 4 → D (Correct Answer)
B. 1 → A, 2 → C, 3 → D, 4 → B
C. 1 → C, 2 → D, 3 → A, 4 → B
D. 1 → C, 2 → A, 3 → D, 4 → B

Explanation: **1 → A, 2 → B, 3 → C, 4 → D** - **Fumarylacetoacetate hydrolase** deficiency causes **Tyrosinemia Type I**, a severe metabolic disorder affecting the liver and kidneys with accumulation of toxic metabolites like succinylacetone. - **Tyrosine transaminase** deficiency leads to **Tyrosinemia Type II** (Richner-Hanhart syndrome), characterized by ocular and cutaneous lesions with elevated plasma tyrosine. - **Tyrosinase** deficiency results in **Albinism** (oculocutaneous albinism type 1), due to lack of melanin production from tyrosine. - **Homogentisate oxidase** deficiency causes **Alkaptonuria**, where homogentisic acid accumulates, turning urine black upon standing and causing ochronosis. *1 → A, 2 → C, 3 → D, 4 → B* - This incorrectly matches tyrosine transaminase with Albinism and tyrosinase with Alkaptonuria, reversing the melanin synthesis pathway enzyme with the tyrosine degradation pathway enzyme. *1 → C, 2 → D, 3 → A, 4 → B* - This incorrectly matches fumarylacetoacetate hydrolase with Albinism (which requires tyrosinase deficiency) and homogentisate oxidase with Tyrosinemia Type II (which requires tyrosine transaminase deficiency). *1 → C, 2 → A, 3 → D, 4 → B* - This incorrectly places the severe hepatorenal disease (Tyrosinemia Type I) with tyrosine transaminase instead of fumarylacetoacetate hydrolase, and mismatches the melanin pathway enzyme with alkaptonuria.

Question 709: Which of the following chromosomes is classified as a Group D chromosome?

A. Chromosome 3
B. Chromosome 6
C. Chromosome 12
D. Chromosome 15 (Correct Answer)

Explanation: ***Chromosome 15*** - **Group D chromosomes** are characterized by their **medium size** and **acrocentric structure**, meaning the centromere is located very close to one end. - Chromosome 15 fits this description along with chromosomes 13 and 14. *Chromosome 3* - This is a **large metacentric chromosome**, meaning its centromere is located in the middle, and it belongs to **Group A**. - Its size and centromere position differentiate it from the acrocentric chromosomes of Group D. *Chromosome 6* - Chromosome 6 is a **medium-sized submetacentric chromosome**, with its centromere slightly off-center, placing it within **Group C**. - This group distinguishes itself from the acrocentric chromosomes of Group D. *Chromosome 12* - Chromosome 12 is also categorized as a **medium-sized submetacentric chromosome**, belonging to **Group C**. - Its centromere position is not near the telomere, unlike the acrocentric chromosomes of Group D.

Question 710: Inheritance associated with congenital adrenal hyperplasia -

A. AR (Correct Answer)
B. AD
C. XR
D. XD

Explanation: ***AR*** - Congenital adrenal hyperplasia (CAH) typically results from deficiencies in enzymes involved in adrenal steroid synthesis, most commonly **21-hydroxylase deficiency**. - These enzyme deficiencies are inherited in an **autosomal recessive (AR)** pattern, meaning an individual must inherit two copies of the defective gene (one from each parent) to manifest the condition. *AD* - **Autosomal dominant (AD)** inheritance means only one copy of a defective gene is needed for the condition to appear. This is not the typical inheritance pattern for CAH. - While some rare forms of adrenal disorders can be AD, the classic presentation of CAH is not. *XR* - **X-linked recessive (XR)** inheritance refers to conditions caused by genes on the X chromosome, primarily affecting males. CAH does not follow this pattern. - Males are generally more severely affected than females in XR disorders, which is not the case for common forms of CAH. *XD* - **X-linked dominant (XD)** inheritance means a single copy of a defective gene on the X chromosome can cause the disorder. This pattern is not characteristic of CAH. - XD disorders often have different presentations in males and females, and CAH does not fit this genetic model.

Practice by Chapter

Single Gene Disorders

Practice Questions

Biochemical Diagnosis of Genetic Disorders

Practice Questions

Inborn Errors of Metabolism

Practice Questions

Lysosomal Storage Diseases

Practice Questions

Glycogen Storage Diseases

Practice Questions

Disorders of Lipoprotein Metabolism

Practice Questions

Disorders of Purine and Pyrimidine Metabolism

Practice Questions

Hemoglobinopathies

Practice Questions

Porphyrias

Practice Questions

Biochemical Markers for Disease Diagnosis

Practice Questions

Newborn Screening for Genetic Disorders

Practice Questions

Enzyme Replacement Therapy

Practice Questions

Want unlimited practice?

Get full access to all questions, explanations, and performance tracking.

Start For Free