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: 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 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: Which chromosome contains the gene responsible for MEN2 (Multiple Endocrine Neoplasia type 2)?

A. 13q11
B. 10q11.2 (Correct Answer)
C. 11q13
D. 11q10.2

Explanation: ***10q11.2*** - The **MEN2 gene** is located on **chromosome 10** at band **q11.2**. - Mutations in this gene, specifically the **RET proto-oncogene**, are responsible for Multiple Endocrine Neoplasia type 2. *11q13* - This chromosomal location is associated with the **MEN1 gene**, which causes Multiple Endocrine Neoplasia type 1. - MEN1 involves tumors of the **parathyroid**, **pancreatic islet cells**, and **anterior pituitary**. *13q11* - This location is not typically associated with the **MEN genes** or other well-known multiple endocrine neoplasia syndromes. - It is more commonly linked to other genetic disorders or specific gene loci unrelated to **endocrine tumor syndromes**. *11q10.2* - This is an incorrect or imprecisely described chromosomal location in the context of Multiple Endocrine Neoplasia syndromes. - While **chromosome 11** is relevant for **MEN1**, the specific band **11q10.2** is not the correct location for either MEN1 or MEN2 genes.

Question 706: 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 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: 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 709: 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.

Question 710: 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.

Practice by Chapter

Single Gene Disorders

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Biochemical Diagnosis of Genetic Disorders

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Inborn Errors of Metabolism

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Lysosomal Storage Diseases

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Glycogen Storage Diseases

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Disorders of Lipoprotein Metabolism

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Disorders of Purine and Pyrimidine Metabolism

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Hemoglobinopathies

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Porphyrias

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Biochemical Markers for Disease Diagnosis

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Newborn Screening for Genetic Disorders

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Enzyme Replacement Therapy

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