Genetic Disorders and Biochemical Pathology — MCQs
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Which of the following is an example of an antiapoptotic gene?
Pruritus [Itching] associated with Congenital Erythropoietic Porphyria is caused by deficiency of -
Which of the following statements about Niemann-Pick disease is false?
Which of the following is caused by congenital 17 hydroxylase deficiency:
3 beta hydroxysteroid dehydrogenase deficiency causes increased production of -
A normal female, whose father is color blind, marries a normal man. What are the chances of their son being color blind?
Hereditary orotic aciduria Type-I is due to deficiency of?
Which organelle is primarily affected in Fabry's disease?
Ochronosis is primarily associated with which condition?
In sickle cell anemia, the mutation at codon 6 results in the substitution of which amino acid?
Genetic Disorders and Biochemical Pathology Indian Medical PG Practice Questions and MCQs
Question 731: Which of the following is an example of an antiapoptotic gene?
- A. FLIP (Correct Answer)
- B. P53
- C. BAX
- D. BIM
Explanation: ***FLIP*** - **FLIP** is an **antiapoptotic gene** that inhibits the activation of caspase-8, thereby blocking the extrinsic apoptotic pathway. - It acts as an **FLICE-inhibitory protein**, preventing the formation of the death-inducing signaling complex (DISC) or its downstream activation. *P53* - **P53** is a **tumor suppressor gene** that promotes apoptosis in response to DNA damage or cellular stress. - It is a **pro-apoptotic gene**, orchestrating cell cycle arrest and apoptosis to prevent the propagation of damaged cells. *BAX* - **BAX** is a **pro-apoptotic gene** belonging to the Bcl-2 family, which promotes the release of cytochrome c from mitochondria. - This release initiates the **intrinsic apoptotic pathway**, leading to caspase activation and cell death. *BIM* - **BIM** is a **pro-apoptotic gene** of the Bcl-2 family, acting as a sensitizer for apoptosis by binding to and inhibiting anti-apoptotic Bcl-2 family proteins. - Its activation leads to the **neutralization of survival factors**, thereby promoting mitochondrial outer membrane permeabilization and apoptosis.
Question 732: Pruritus [Itching] associated with Congenital Erythropoietic Porphyria is caused by deficiency of -
- A. Uroporphyrinogen - III synthase (Correct Answer)
- B. Uroporphyrinogen - I synthase
- C. 5-ALA dehydratase
- D. HMB synthase
Explanation: ***Uroporphyrinogen - III synthase*** - Congenital Erythropoietic Porphyria (CEP) is caused by a **deficiency of uroporphyrinogen III synthase**, leading to the accumulation of uroporphyrinogen I and coproporphyrinogen I. - These accumulated **Type I porphyrinogens** are non-functional in heme synthesis and are highly **photoreactive**, causing the characteristic photosensitivity and skin symptoms, including intense pruritus. *5-ALA dehydratase* - Deficiency of **5-ALA dehydratase** (also known as porphobilinogen synthase) is associated with **ALA dehydratase deficiency porphyria (ADP)**, a very rare acute hepatic porphyria. - Symptoms primarily involve **neurovisceral attacks** and do not typically include pruritus or photosensitivity. *Uroporphyrinogen - I synthase* - **Uroporphyrinogen I synthase** is an outdated and incorrect term; the correct enzyme in the heme synthesis pathway is **hydroxymethylbilane synthase (HMB synthase)** or **porphobilinogen deaminase (PBG deaminase)**, which synthesizes HMB. - Deficiency in HMB synthase leads to **acute intermittent porphyria (AIP)**, characterized by acute neurological attacks, not severe pruritus. *HMB synthase* - **HMB synthase** (hydroxymethylbilane synthase), also known as **porphobilinogen deaminase (PBG deaminase)**, is deficient in **acute intermittent porphyria (AIP)**. - AIP is marked by intermittent neurological dysfunction and abdominal pain, with **no significant photosensitivity or pruritus**.
Question 733: Which of the following statements about Niemann-Pick disease is false?
- A. Due to deficiency of sphingomyelinase.
- B. CNS symptoms are present in type A.
- C. Type B Niemann-Pick disease is characterized by severe neurological symptoms. (Correct Answer)
- D. Histiocytes show PAS positive inclusions, and Type A is more severe.
Explanation: ***Type B Niemann-Pick disease is characterized by severe neurological symptoms.*** - This statement is **false** because **Type B Niemann-Pick disease** generally presents with **visceral involvement** (e.g., hepatosplenomegaly, lung disease) with **minimal to no neurological symptoms**. - **Severe neurological symptoms** are characteristic of **Type A Niemann-Pick disease**, which involves widespread CNS degeneration and a more rapidly progressive course. *Due to deficiency of sphingomyelinase.* - This statement is **true**. - Niemann-Pick disease (Types A and B) is caused by a deficiency of the enzyme **acid sphingomyelinase**, leading to the accumulation of sphingomyelin within lysosomes, particularly in macrophages. *CNS symptoms are present in type A.* - This statement is **true**. - **Type A Niemann-Pick disease** is the most severe form and is characterized by significant **neurodegeneration** in addition to visceral involvement. - Patients typically present with **developmental regression**, **ataxia**, and **spasticity** due to extensive sphingomyelin deposition in the central nervous system. *Histiocytes show PAS positive inclusions, and Type A is more severe.* - This statement is **true**. - The characteristic "foam cells" (lipid-laden macrophages/histiocytes) found in tissues of Niemann-Pick patients stain positive with **periodic acid–Schiff (PAS)** due to accumulated sphingomyelin. - **Type A Niemann-Pick disease** is indeed the most severe form, with a rapidly progressive course and early fatality, usually by early childhood.
Question 734: Which of the following is caused by congenital 17 hydroxylase deficiency:
- A. Hypertension (Correct Answer)
- B. Delayed sexual development
- C. Ambiguous genitalia in males
- D. Hypokalemia
Explanation: ***Hypertension*** - **17-hydroxylase deficiency** causes a unique combination among congenital adrenal hyperplasia (CAH) variants: **hypertension with sexual infantilism**. - The enzyme block shunts steroid synthesis toward the mineralocorticoid pathway, leading to excessive **deoxycorticosterone (DOC)** and **corticosterone** production. - Elevated DOC causes **sodium retention**, **volume expansion**, and **hypertension** — this distinguishes it from other CAH forms (like 21-hydroxylase deficiency, which causes hypotension). - **Hypertension is the key diagnostic feature** that differentiates this from other causes of sexual infantilism. *Hypokalemia* - Also a **characteristic feature** of 17-hydroxylase deficiency, caused by the same mineralocorticoid excess (DOC). - The elevated DOC promotes **potassium wasting** in the renal tubules. - However, **hypertension** is typically considered the primary distinguishing feature, with hypokalemia as an associated finding. *Delayed sexual development* - This is a **major manifestation** of 17-hydroxylase deficiency due to impaired synthesis of **both androgens and estrogens**. - Presents as **primary amenorrhea** and absent secondary sexual characteristics in 46,XX females. - Presents as **sexual infantilism** in 46,XY individuals with female external genitalia. - While this is indeed caused by the deficiency, the question focuses on the **distinguishing biochemical feature** (hypertension with hypokalemia). *Ambiguous genitalia in males* - **Genetically male (46,XY) individuals** with 17-hydroxylase deficiency typically have **female or ambiguous external genitalia** due to lack of testosterone synthesis. - This represents **undervirilization** rather than virilization. - Like delayed sexual development, this is a cardinal feature, but **hypertension** is the biochemical hallmark that distinguishes this CAH variant from others.
Question 735: 3 beta hydroxysteroid dehydrogenase deficiency causes increased production of -
- A. DHEA (Correct Answer)
- B. Progesterone
- C. Deoxycortisol
- D. Estradiol
Explanation: ***DHEA*** - The enzyme **3 beta-hydroxysteroid dehydrogenase (3β-HSD)** is crucial for converting **delta-5 steroids (pregnenolone, 17-OH-pregnenolone, and DHEA)** into **delta-4 steroids (progesterone, 17-OH-progesterone, and androstenedione)**. - A **deficiency** in 3β-HSD leads to the accumulation of its substrates, particularly **DHEA (dehydroepiandrosterone)** and **17-OH-pregnenolone**, due to the impaired conversion in the steroid synthesis pathway. - Among the accumulated substrates, **DHEA** has weak androgenic activity, making it clinically significant in this enzyme deficiency. *Progesterone* - **Progesterone** is a delta-4 steroid, which is synthesized from **pregnenolone** via the action of **3β-HSD**. - A deficiency in this enzyme would **decrease** the production of progesterone, not increase it, as the enzyme is required for its synthesis. *Deoxycortisol* - **Deoxycortisol (11-deoxycortisol)** is a precursor to cortisol, formed later in the adrenal steroid synthesis pathway from **17-hydroxyprogesterone**. - Its production would be **decreased** by a 3β-HSD deficiency, as the pathway is blocked upstream, reducing the formation of downstream products like cortisol and its precursors. *Estradiol* - **Estradiol** is an estrogen, synthesized from androgens (like testosterone) via the enzyme **aromatase**. - A deficiency in 3β-HSD would impair the production of androgens like androstenedione and testosterone, which are precursors for estradiol, thereby leading to a **decrease** in estradiol levels, not an increase.
Question 736: A normal female, whose father is color blind, marries a normal man. What are the chances of their son being color blind?
- A. 25%
- B. 50% (Correct Answer)
- C. 75%
- D. No chance
Explanation: ***50%*** - The mother is a **carrier** because her father is colorblind, meaning she has one normal X chromosome and one affected X chromosome. - A son inherits his X chromosome from his mother; there is a **50% chance** that he will inherit the X chromosome carrying the colorblindness gene. *25%* - This percentage is typically associated with **autosomal recessive** inheritance patterns, not X-linked traits like colorblindness. - It would imply a different genetic setup for the parents than described, such as both parents being carriers for an autosomal recessive condition. *75%* - This probability would suggest a more complex genetic scenario or a condition with **incomplete penetrance** or a dominant inheritance pattern, which does not apply to X-linked recessive colorblindness in this context. - It does not align with the mendelian inheritance pattern for X-linked recessive traits when the mother is a carrier and the father is unaffected. *No chance* - This would only be true if the mother was **not a carrier** of the colorblindness gene. - Since her father was colorblind, she must have inherited his affected X chromosome, making her an obligate carrier.
Question 737: Hereditary orotic aciduria Type-I is due to deficiency of?
- A. Orotate phosphoribosyl transferase
- B. UMP synthase (Correct Answer)
- C. Orotic acid decarboxylase
- D. All of the options
Explanation: ***UMP synthase*** - Hereditary orotic aciduria Type-I is caused by a deficiency of the **bifunctional enzyme UMP synthase** (also called UMP synthase complex). - UMP synthase catalyzes two sequential reactions in the *de novo* pyrimidine synthesis pathway: 1. **OPRT activity**: Converts orotate → orotidine 5'-monophosphate (OMP) 2. **ODC activity**: Converts OMP → uridine 5'-monophosphate (UMP) - This is the **most precise and complete answer** as it identifies the actual enzyme complex that is deficient. - **Clinical features**: Megaloblastic anemia, growth retardation, immunodeficiency; responds to oral uridine supplementation. *Orotate phosphoribosyl transferase* - This represents only **one of the two catalytic activities** of the UMP synthase enzyme (the first step). - While this activity is indeed deficient in Type-I orotic aciduria, naming only this activity is **incomplete** because the enzyme has two functions. - This would be a **partial answer** rather than the complete enzyme name. *Orotic acid decarboxylase* - This represents only **the second catalytic activity** of the UMP synthase enzyme (converts OMP to UMP). - Like OPRT, this activity is also deficient, but naming only this component is **incomplete**. - **Type II orotic aciduria** (extremely rare) involves isolated ODC deficiency without OPRT deficiency. *All of the options* - While technically both OPRT and ODC activities are affected in Type-I orotic aciduria, the **standard nomenclature** refers to the deficient enzyme as **"UMP synthase"** - the name of the complete bifunctional enzyme. - In medical terminology and examination context, we identify enzyme deficiencies by the **name of the enzyme complex**, not by listing all its individual catalytic activities. - Therefore, **"UMP synthase"** is the single most accurate and complete answer.
Question 738: Which organelle is primarily affected in Fabry's disease?
- A. Endoplasmic Reticulum
- B. Lysosome (Correct Answer)
- C. Golgi apparatus
- D. Cell membrane
Explanation: ***Lysosome*** - Fabry's disease is a **lysosomal storage disorder** caused by a deficiency of the enzyme **alpha-galactosidase A**. - This enzyme deficiency leads to the accumulation of **globotriaosylceramide (Gb3)** within lysosomes in various cells throughout the body. *Endoplasmic Reticulum* - The **endoplasmic reticulum** is involved in protein synthesis and folding, and lipid metabolism. - While cellular stress from Gb3 accumulation can indirectly affect the ER, it is not the primary organelle involved in the storage of the accumulated substrate in Fabry's disease. *Golgi apparatus* - The **Golgi apparatus** modifies, sorts, and packages proteins and lipids. - It is not the site of primary pathology or substrate accumulation in lysosomal storage diseases. *Cell membrane* - The **cell membrane** regulates passage of substances into and out of the cell. - While lysosomal dysfunction can ultimately impact overall cell function, the cell membrane itself is not the organelle where the undigested substrate accumulates in Fabry's disease.
Question 739: Ochronosis is primarily associated with which condition?
- A. Carbolic acid (phenol) poisoning
- B. Hydrochloric acid poisoning
- C. Oxalic acid poisoning
- D. Alkaptonuria (Correct Answer)
Explanation: ***Alkaptonuria*** - **Ochronosis** is a rare genetic disorder characterized by the accumulation of **homogentisic acid** in connective tissues, leading to a blue-black discoloration; this is the defining feature of alkaptonuria. - Patients with alkaptonuria lack the enzyme **homogentisate 1,2-dioxygenase**, preventing the breakdown of homogentisic acid and causing its buildup. *Hydrochloric acid poisoning* - This condition involves the ingestion of **corrosive acid**, leading to severe burns and tissue damage in the gastrointestinal tract. - It does not cause the characteristic **pigmentation** and systemic connective tissue involvement seen in ochronosis. *Carbolic acid (phenol) poisoning* - **Phenol poisoning** is a toxic emergency characterized by widespread protein denaturation and tissue damage. - It results in systemic toxicity, including cardiovascular and renal effects, but not the **blue-black discoloration of connective tissues** associated with ochronosis. *Oxalic acid poisoning* - **Oxalic acid poisoning** can lead to severe metabolic disturbance, including hypocalcemia due to calcium oxalate formation, and acute renal failure. - It is not associated with the **hereditary metabolic defect** or the unique pattern of pigmentation that defines ochronosis.
Question 740: In sickle cell anemia, the mutation at codon 6 results in the substitution of which amino acid?
- A. Valine for glutamic acid (Correct Answer)
- B. Isoleucine for valine
- C. Valine for isoleucine
- D. Glutamic acid for valine
Explanation: ***Valine for glutamic acid*** - In **sickle cell anemia**, the normal **glutamic acid** at codon 6 of the $\beta$-globin chain is replaced by **valine**. - This single amino acid substitution is responsible for the abnormal **hemoglobin S (HbS)** and the characteristic sickling of red blood cells. *Isoleucine for valine* - This substitution is **not characteristic** of sickle cell anemia. - While other hemoglobinopathies exist, this specific change does not lead to the sickle cell phenotype. *Valine for isoleucine* - This substitution is **not the primary genetic defect** found in sickle cell anemia. - The mutation in sickle cell anemia involves the replacement of a negatively charged amino acid with a neutral one. *Glutamic acid for valine* - This represents the **reverse substitution** of what occurs in sickle cell anemia. - In sickle cell, valine replaces glutamic acid, not the other way around.
Practice by Chapter
Single Gene Disorders
Practice Questions
Biochemical Diagnosis of Genetic Disorders
Practice Questions
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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