Genetic Disorders and Biochemical Pathology Practice Questions

Q: Hereditary orotic aciduria Type-I is due to deficiency of?

UMP synthase. ***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.

Q: A normal female, whose father is color blind, marries a normal man. What are the chances of their son being color blind?

50%. ***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.

Q: Which organelle is primarily affected in Fabry's disease?

Lysosome. ***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.

Q: Ochronosis is primarily associated with which condition?

Alkaptonuria. ***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.

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: Conjugated hyperbilirubinemia is seen in which of the following conditions?

Dubin-Johnson syndrome. ***Dubin-Johnson syndrome*** - This is an **autosomal recessive disorder** characterized by a defect in the excretion of **conjugated bilirubin** from hepatocytes into the bile canaliculi due to mutation in the **MRP2 (ABCC2) gene**. - It leads to a **direct (conjugated) hyperbilirubinemia** causing recurrent episodes of **jaundice**, and often a characteristic **black liver** due to melanin-like pigment accumulation. - Typically presents in **adolescence or early adulthood** with mild, fluctuating jaundice. *Gilbert syndrome* - This is a common, benign, **hereditary condition** characterized by intermittently elevated levels of **unconjugated (indirect) bilirubin**. - It results from a partial deficiency of the enzyme **uridine diphosphate glucuronosyltransferase (UGT1A1)**, responsible for bilirubin conjugation. - Presents with mild jaundice during fasting, stress, or illness. *Crigler-Najjar syndrome* - This is a rare, severe, **hereditary disorder** involving a complete (Type I) or near-complete (Type II) deficiency of **UGT1A1 enzyme** activity. - It leads to very high levels of **unconjugated hyperbilirubinemia**, with Type I causing severe **kernicterus** and often death in infancy if untreated. *None of the options* - Since **Dubin-Johnson syndrome** is a well-established cause of conjugated hyperbilirubinemia, this option is incorrect.

Q: Gaucher's disease is:

Autosomal recessive inheritance. ***Autosomal recessive inheritance*** - **Gaucher's disease** is caused by a deficiency of the enzyme **glucocerebrosidase**, leading to the accumulation of glucocerebroside in macrophages. - This genetic disorder requires two copies of the defective gene (one from each parent) to manifest, which is characteristic of **autosomal recessive inheritance**. *Autosomal dominant inheritance* - In **autosomal dominant inheritance**, only one copy of the defective gene is needed for the disease to occur, which is not the case for Gaucher's disease. - Affected individuals usually have at least one affected parent, and there is a 50% chance of passing the condition to offspring. *X-linked recessive inheritance* - **X-linked recessive inheritance** primarily affects males, as the gene is located on the X chromosome. - Females are typically carriers and are less commonly affected, which does not describe the inheritance pattern of Gaucher's disease. *X-linked dominant inheritance* - **X-linked dominant inheritance** means the disease can affect both males and females, but females are typically more mildly affected. - All daughters of an affected father will inherit the condition, which is not consistent with Gaucher's disease.

Q: Which of the following porphyrias is not inherited as an autosomal dominant disorder?

Congenital Erythropoietic Porphyria. ***Congenital Erythropoietic Porphyria*** - This porphyria is inherited in an **autosomal recessive** pattern, meaning two copies of the defective gene (one from each parent) are required for the disease to manifest. - It results from a deficiency in **uroporphyrinogen III synthase (URO-synthase)**, leading to the accumulation of uroporphyrinogen I and coproporphyrinogen I isomers. *Acute Intermittent Porphyria* - This is an **autosomal dominant** disorder caused by a deficiency in **hydroxymethylbilane synthase (HMBS)**, also known as porphyrobilinogen deaminase (PBG deaminase). - It primarily affects the nervous system, leading to acute neurovisceral attacks. *Porphyria Cutanea Tarda* - This is **primarily sporadic (acquired)** in about 80% of cases, often associated with hepatic iron overload, alcohol use, hepatitis C, or estrogen use. - Only about 20% of cases are familial with **autosomal dominant** inheritance pattern. - It is caused by a deficiency in **uroporphyrinogen decarboxylase (UROD)**, leading to photosensitivity due to accumulated porphyrins in the skin. *Hereditary Coproporphyria* - This is an **autosomal dominant** disorder caused by a deficiency in **coproporphyrinogen oxidase (CPOX)**. - It can present with both neurovisceral attacks and photosensitivity, depending on the accumulated porphyrins.

Question 1

Hereditary orotic aciduria Type-I is due to deficiency of?

Accepted Answer

UMP synthase

Answer

Orotate phosphoribosyl transferase

Answer

Orotic acid decarboxylase

Answer

All of the options

Question 2

A normal female, whose father is color blind, marries a normal man. What are the chances of their son being color blind?

Accepted Answer

50%

Answer

25%

Answer

75%

Answer

No chance

Question 3

Which organelle is primarily affected in Fabry's disease?

Accepted Answer

Lysosome

Answer

Endoplasmic Reticulum

Answer

Golgi apparatus

Answer

Cell membrane

Question 4

Ochronosis is primarily associated with which condition?

Accepted Answer

Alkaptonuria

Answer

Carbolic acid (phenol) poisoning

Answer

Hydrochloric acid poisoning

Answer

Oxalic acid poisoning

Question 5

Hunter syndrome is due to deficiency of which enzyme?

Accepted Answer

Iduronate-2-sulfatase

Answer

Beta galactosidase

Answer

Sphingomyelinase

Answer

Hyaluronidase

Question 6

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 7

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 8

Conjugated hyperbilirubinemia is seen in which of the following conditions?

Accepted Answer

Dubin-Johnson syndrome

Answer

Gilbert syndrome

Answer

Crigler-Najjar syndrome

Answer

None of the options

Question 9

Gaucher's disease is:

Accepted Answer

Autosomal recessive inheritance

Answer

Autosomal dominant inheritance

Answer

X-linked recessive inheritance

Answer

X-linked dominant inheritance

Question 10

Which of the following porphyrias is not inherited as an autosomal dominant disorder?

Accepted Answer

Congenital Erythropoietic Porphyria

Answer

Porphyria Cutanea Tarda

Answer

Hereditary Coproporphyria

Answer

Acute Intermittent Porphyria

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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