Genetic Disorders and Biochemical Pathology Practice Questions

Q: Hunter syndrome is due to deficiency of which enzyme?

Iduronate-2-sulfatase. ***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.

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

50% chance of being affected. ***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.

Q: What is the metabolic abnormality associated with Zellweger syndrome?

Accumulation of very long-chain fatty acids. ***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.**

Q: What is the primary biochemical defect in alkaptonuria?

Deficiency of homogentisate 1,2-dioxygenase. ***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.

Q: In sickle cell anemia, the mutation at codon 6 results in the substitution of which amino acid?

Valine for glutamic acid. ***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.

Q: Ochronosis is due to accumulation of ?

Homogentisic acid. ***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.

Q: Acute intermittent porphyria is due to deficiency of?

Porphobilinogen deaminase. ***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.

Q: Male to male transmission is seen in -

Autosomal dominant diseases. ***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.

Q: The gene known to be associated with cataract is

CRYAA. ***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.

Question 1

Hunter syndrome is due to deficiency of which enzyme?

Accepted Answer

Iduronate-2-sulfatase

Answer

Beta galactosidase

Answer

Sphingomyelinase

Answer

Hyaluronidase

Question 2

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

Accepted Answer

50% chance of being affected

Answer

25% chance of being affected

Answer

100% chance of being affected

Answer

75% chance of being affected

Question 3

What is the metabolic abnormality associated with Zellweger syndrome?

Accepted Answer

Accumulation of very long-chain fatty acids

Answer

Accumulation of long-chain fatty acids

Answer

Accumulation of short-chain fatty acids

Answer

Accumulation of medium-chain fatty acids

Question 4

What is the primary biochemical defect in alkaptonuria?

Accepted Answer

Deficiency of homogentisate 1,2-dioxygenase

Answer

FeCl3 test is negative

Answer

Urine turns black immediately upon voiding

Answer

Benedict's test is diagnostic for alkaptonuria

Question 5

In sickle cell anemia, the mutation at codon 6 results in the substitution of which amino acid?

Accepted Answer

Valine for glutamic acid

Answer

Isoleucine for valine

Answer

Valine for isoleucine

Answer

Glutamic acid for valine

Question 6

Ochronosis is due to accumulation of ?

Accepted Answer

Homogentisic acid

Answer

Phenylpyruvate

Answer

Xanthurenate

Answer

Glyoxylate

Question 7

Acute intermittent porphyria is due to deficiency of?

Accepted Answer

Porphobilinogen deaminase

Answer

Uroporphyrinogen III synthase

Answer

Ferrochelatase

Answer

ALA synthase

Question 8

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

Accepted Answer

Carrier mothers have a 50% chance of transmitting the disease to their sons

Answer

Fathers can transmit X-linked traits to their sons

Answer

25% of sons of a carrier mother are affected

Answer

100% of daughters of a diseased father are affected

Question 9

Male to male transmission is seen in -

Accepted Answer

Autosomal dominant diseases

Answer

Autosomal recessive

Answer

X-linked dominant

Answer

Mitochondrial disease

Question 10

The gene known to be associated with cataract is

Accepted Answer

CRYAA

Answer

PAX6

Answer

FKHL7

Answer

CYP1B1

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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