Genetic Disorders and Biochemical Pathology — MCQs

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

Question 741: Which of the following statements about the inheritance of an X-linked recessive trait is true?

A. Fathers can transmit X-linked traits to their sons
B. 25% of sons of a carrier mother are affected
C. Carrier mothers have a 50% chance of transmitting the disease to their sons (Correct Answer)
D. 100% of daughters of a diseased father are affected

Explanation: ***Carrier mothers have a 50% chance of transmitting the disease to their sons*** - A mother who is a carrier for an **X-linked recessive trait** has one normal X chromosome and one X chromosome carrying the recessive allele. - Each son she has has a **50% chance** of inheriting the X chromosome with the recessive allele (and thus being affected) and a 50% chance of inheriting the normal X chromosome. *Fathers can transmit X-linked traits to their sons* - Fathers transmit their **Y chromosome** to their sons, not an X chromosome. - Therefore, fathers cannot directly transmit X-linked traits to their sons. *25% of sons of a carrier mother are affected* - This statement is incorrect; as explained above, a carrier mother has a **50% chance** of transmitting the affected X chromosome to each son. - The 25% probability typically applies to autosomal recessive inheritance, not X-linked. *100% of daughters of a diseased father are affected* - A diseased father (meaning he has the **X-linked recessive trait**) will pass his single X chromosome to all of his daughters. - Therefore, all his daughters will be **obligate carriers**, but they will only be affected if their mother also contributes an X chromosome with the recessive allele (which is rare for recessive traits).

Question 742: If the mother is affected and the father is not, in an autosomal dominant disease, what is the chance of their children being affected?

A. 50% chance of being affected (Correct Answer)
B. 25% chance of being affected
C. 100% chance of being affected
D. 75% chance of being affected

Explanation: ***50% chance of being affected*** - In an **autosomal dominant (AD)** disease, only one copy of the **affected gene** is needed for the disease to manifest. - If the mother is affected (heterozygous, Aa) and the father is unaffected (homozygous recessive, aa), their offspring have a **50% chance** of inheriting the dominant affected allele (A) from the mother. *25% chance of being affected* - A 25% chance of being affected is typical for **autosomal recessive** inheritance when both parents are **heterozygous carriers**. - This scenario involves an autosomal dominant trait, where the inheritance pattern is different. *100% chance of being affected* - This would only occur if the mother were **homozygous dominant (AA)** and the father were unaffected (aa), where all offspring would inherit one dominant allele. - In typical autosomal dominant pedigrees, affected individuals are **heterozygous (Aa)**, leading to a 50% risk for each child. *75% chance of being affected* - A 75% chance is not characteristic of simple autosomal dominant inheritance for a cross between an affected heterozygous individual and an unaffected individual. - This outcome would occur if both parents were heterozygous (Aa × Aa), which is not the scenario described in this question.

Question 743: Mutation in GLUT-2 causes which syndrome?

A. Dandy walker syndrome
B. Beckwith-Wiedemann syndrome
C. Menke's disease
D. Fanconi-Bickel syndrome (Correct Answer)

Explanation: ***Fanconi-Bickel syndrome*** - This syndrome is caused by a **mutation in the GLUT-2 gene**, leading to dysfunctional glucose transport in the liver, kidneys, and intestines. - Key features include **hepatorenal glycogen accumulation**, **renal tubulopathy** (Fanconi syndrome), and **impaired glucose and galactose utilization**. *Dandy-Walker syndrome* - This is a **congenital brain malformation** involving the cerebellum and fourth ventricle. - It is often associated with hydrocephalus, but not directly linked to glucose transporter defects. *Beckwith-Wiedemann syndrome* - This is an **overgrowth disorder** characterized by a high risk of childhood cancer and congenital anomalies. - It is primarily caused by genetic abnormalities on **chromosome 11p15.5** and is unrelated to GLUT-2 mutations. *Menke's disease* - This is a rare X-linked recessive disorder of **copper metabolism**, leading to severe neurological degeneration. - It results from mutations in the **ATP7A gene**, which encodes a copper-transporting ATPase.

Question 744: Hunter syndrome is due to deficiency of which enzyme?

A. Beta galactosidase
B. Sphingomyelinase
C. Hyaluronidase
D. Iduronate-2-sulfatase (Correct Answer)

Explanation: ***Iduronate-2-sulfatase*** - **Hunter syndrome** (Mucopolysaccharidosis Type II) is caused by a deficiency of the enzyme **iduronate-2-sulfatase**. - This deficiency leads to the accumulation of **dermatan sulfate** and **heparan sulfate** within lysosomes. *Beta galactosidase* - Deficiency of **beta-galactosidase** is associated with **GM1 gangliosidosis** and **Morquio syndrome type B**. - These conditions present with different clinical features, including neurological degeneration and skeletal abnormalities, not consistent with Hunter syndrome. *Sphingomyelinase* - A deficiency in **sphingomyelinase** causes **Niemann-Pick disease types A and B**. - This leads to the accumulation of **sphingomyelin** in various organs, resulting in hepatosplenomegaly, neurodegeneration, and lung disease. *Hyaluronidase* - **Hyaluronidase** is an enzyme that breaks down hyaluronic acid, which is a component of the extracellular matrix. - While it has various roles in the body and is sometimes used clinically, its deficiency is not associated with Hunter syndrome or a specific lysosomal storage disease.

Question 745: Male to male transmission is seen in -

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

Explanation: ***Autosomal dominant diseases*** - **Autosomal dominant** inheritance patterns involve a gene located on one of the **autosomes**, meaning it is not sex-linked. - Therefore, a father carrying an autosomal dominant gene can pass it to both sons and daughters with a **50% probability** for each child. - **Male-to-male transmission** is a hallmark feature that helps distinguish autosomal dominant from X-linked inheritance patterns. *Autosomal recessive* - **Autosomal recessive** diseases require **two copies** of the mutated gene (one from each parent) for the disease to manifest. - While a father can pass a recessive allele to his son, male-to-male transmission of the **disease phenotype** requires the mother to also be at least a carrier, making it not a defining feature of this inheritance pattern. - The key characteristic is horizontal pattern (affected siblings) rather than vertical transmission. *X-linked dominant* - In **X-linked dominant** inheritance, affected fathers **cannot** transmit the trait to their sons because sons inherit their **X chromosome** from their mother and their Y chromosome from their father. - All daughters of an affected father will inherit the affected X chromosome and thus the disease. - **Absence of male-to-male transmission** is a key distinguishing feature. *Mitochondrial disease* - **Mitochondrial diseases** are inherited exclusively from the **mother** to all her children, regardless of their sex. - Fathers with mitochondrial disease cannot transmit the condition to any of their children. - This shows **maternal inheritance only**, with no paternal transmission possible.

Question 746: Ochronosis is due to accumulation of ?

A. Homogentisic acid (Correct Answer)
B. Phenylpyruvate
C. Xanthurenate
D. Glyoxylate

Explanation: ***Homogentisic acid*** - Ochronosis is a condition caused by the excessive accumulation of **homogentisic acid** in connective tissues. - This accumulation occurs due to a deficiency of the enzyme **homogentisate 1,2-dioxygenase** (HGD), which is responsible for breaking down homogentisic acid in the tyrosine degradation pathway. *Phenylpyruvate* - **Phenylpyruvate** accumulates in **phenylketonuria (PKU)**, a different metabolic disorder where there's a deficiency in phenylalanine hydroxylase. - PKU leads to intellectual disability and other neurological problems, not the characteristic pigmentation and arthritis of ochronosis. *Xanthurenate* - **Xanthurenate** is an abnormal metabolite of tryptophan metabolism that can accumulate in **vitamin B6 deficiency**. - Its accumulation is associated with increased urinary excretion and is not directly implicated in the pathology of ochronosis. *Glyoxylate* - **Glyoxylate** is involved in various metabolic pathways, and its accumulation (or accumulation of its metabolic products like oxalate) is associated with **primary hyperoxaluria**. - Primary hyperoxaluria leads to kidney stones and kidney failure, a condition distinct from ochronosis.

Question 747: What is the primary biochemical defect in alkaptonuria?

A. FeCl3 test is negative
B. Urine turns black immediately upon voiding
C. Benedict's test is diagnostic for alkaptonuria
D. Deficiency of homogentisate 1,2-dioxygenase (Correct Answer)

Explanation: ***Deficiency of homogentisate 1,2-dioxygenase*** - **Alkaptonuria** is an autosomal recessive disorder caused by the deficiency of **homogentisate 1,2-dioxygenase**, an enzyme in the **tyrosine degradation pathway**. - This deficiency leads to the accumulation of **homogentisic acid** in the body, which is excreted in urine and deposited in connective tissues. *Urine turns black immediately upon voiding* - While urine in alkaptonuria does **turn black**, it typically darkens upon **standing** and exposure to air, not immediately upon voiding. - The darkening is due to the oxidation of accumulated **homogentisic acid**. *FeCl3 test is negative* - The **ferric chloride (FeCl3) test** typically yields a **positive result** (transient green color) in the presence of homogentisic acid in the urine. - Therefore, a negative result would argue against a diagnosis of alkaptonuria. *Benedict's test is diagnostic for alkaptonuria* - **Benedict's test** is used to detect reducing sugars like glucose in urine and would not be used to diagnose alkaptonuria. - A positive Benedict's test in alkaptonuria is due to the reducing properties of homogentisic acid, but it is not specific or diagnostic.

Question 748: What is the metabolic abnormality associated with Zellweger syndrome?

A. Accumulation of long-chain fatty acids
B. Accumulation of short-chain fatty acids
C. Accumulation of very long-chain fatty acids (Correct Answer)
D. Accumulation of medium-chain fatty acids

Explanation: ***Accumulation of very long-chain fatty acids*** - **Zellweger syndrome** is a peroxisomal biogenesis disorder, meaning that peroxisomes, which are responsible for the **beta-oxidation** of very long-chain fatty acids (VLCFAs), are absent or dysfunctional. - The inability to break down **VLCFAs** leads to their accumulation in various tissues, causing significant neurological and systemic dysfunction. *Accumulation of long-chain fatty acids* - While peroxisomes can contribute to the metabolism of some **long-chain fatty acids (LCFAs)**, their primary role in this context is with **VLCFAs**. - **Mitochondria** are the main organelles responsible for the beta-oxidation of most LCFAs. *Accumulation of short-chain fatty acids* - **Short-chain fatty acids (SCFAs)** are primarily produced by gut bacteria and are metabolized in the mitochondria and other cellular compartments. - Their accumulation is not characteristic of **Zellweger syndrome**. *Accumulation of medium-chain fatty acids* - **Medium-chain fatty acids (MCFAs)** are primarily metabolized in the **mitochondria** and do not typically accumulate in Zellweger syndrome. - Disorders affecting MCFA metabolism usually point to different enzyme deficiencies, such as **MCAD deficiency.**

Question 749: Acute intermittent porphyria is due to deficiency of?

A. Porphobilinogen deaminase (Correct Answer)
B. Uroporphyrinogen III synthase
C. Ferrochelatase
D. ALA synthase

Explanation: ***Porphobilinogen deaminase*** - **Acute intermittent porphyria (AIP)** results from a deficiency in **porphobilinogen deaminase** (also known as hydroxymethylbilane synthase). - This enzyme deficiency leads to the accumulation of **aminolevulinic acid (ALA)** and **porphobilinogen (PBG)**, which are neurotoxic and cause the characteristic symptoms of AIP. *Uroporphyrinogen III synthase* - A deficiency in **uroporphyrinogen III synthase** causes **congenital erythropoietic porphyria (Günther disease)**, which is characterized by severe photosensitivity and hemolytic anemia. - This enzyme defect leads to the accumulation of uroporphyrinogen I and coproporphyrinogen I, not the ALA and PBG associated with AIP. *Ferrochelatase* - Deficiency in **ferrochelatase** causes **erythropoietic protoporphyria (EPP)**, which presents with photosensitivity and chronic liver disease due to the accumulation of **protoporphyrin**. - This condition does not cause the acute neurological attacks seen in AIP. *ALA synthase* - **ALA synthase** is the **rate-limiting enzyme** in heme synthesis; while its activity is crucial, a congenital *deficiency* is not the cause of AIP. - Instead, the *upregulation* of ALA synthase activity in AIP (due to the PBG deaminase block) contributes to the accumulation of ALA and PBG.

Question 750: The gene known to be associated with cataract is

A. PAX6
B. FKHL7
C. CRYAA (Correct Answer)
D. CYP1B1

Explanation: ***CRYAA*** - The **CRYAA (crystallin alpha A)** gene is a significant contributor to both congenital and age-related cataracts. - Mutations in **crystallin genes** disrupt the normal structure and transparency of the lens proteins, leading to opacification. - CRYAA is one of the most commonly implicated crystallin genes in hereditary cataract formation. *PAX6* - **PAX6** is a master control gene for eye development and is primarily associated with **aniridia**, a condition characterized by a partial or complete absence of the iris. - While aniridia can be associated with secondary cataracts, PAX6 mutations are not a direct cause of primary cataract formation. *FKHL7* - This gene is more commonly referred to as **FOXC1** and is implicated in **ocular anterior segment dysgenesis**, such as **Axenfeld-Rieger syndrome**. - These conditions can lead to glaucoma and other ocular anomalies but are not directly linked to cataract as their primary presentation in the way crystallin genes are. *CYP1B1* - The **CYP1B1** gene is most notably associated with **primary congenital glaucoma**, particularly in individuals of Arab and Gypsy descent. - Mutations in this gene affect the development of the aqueous humor outflow pathways, leading to elevated intraocular pressure and optic nerve damage, not primarily cataract.

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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