Genetics and Disease Practice Questions

Q: Not true about blue sclera

Seen in Marfan's syndrome. ***Seen in Marfan's syndrome*** - **Blue sclera** is not a characteristic feature of **Marfan's syndrome**. - Marfan's syndrome is primarily associated with **connective tissue abnormalities** affecting the heart, blood vessels, eyes (lens dislocation), and skeleton, but not typically blue sclera. *Blue colour is produced by underlying uveal pigment* - The blue appearance of the sclera is due to the **thinness of the scleral collagen**, allowing the underlying **dark choroidal pigment** (part of the uvea) to be more visible. - This transparency effect is sometimes enhanced by the presence of **sub-scleral fat**, which reflects blue light. *Seen in osteogenesis imperfecta* - **Osteogenesis imperfecta** is a genetic disorder characterized by **brittle bones** and **blue sclera**. - The blue color is due to the **thinning of the sclera**, allowing the underlying choroidal veins to show through. *Not seen in Ehlers-Danlos syndrome* - **Blue sclera** can indeed be a feature of **Ehlers-Danlos syndrome**, particularly in types associated with **collagen defects** [1]. - Like osteogenesis imperfecta, the thinned sclera allows the underlying **choroid** to become visible, creating the blue hue [1].

Q: A patient taken for surgery was given suxamethonium, following which his body temperature began to rise quickly. Along with this he also developed masseter spasm, tachycardia and arrhythmia. An ABG analysis also revealed that he has hypoxia, hypercarbia and acidosis. What is the mode of inheritance of the condition described above?

Autosomal dominant. ***Autosomal dominant*** - This clinical scenario describes **malignant hyperthermia**, a life-threatening pharmacological emergency triggered by certain anesthetic agents like **suxamethonium** and volatile anesthetics. - Malignant hyperthermia is most commonly caused by mutations in the **RYR1 gene**, which codes for the ryanodine receptor, and is inherited in an **autosomal dominant** pattern [1]. *Autosomal recessive* - While some genetic conditions are inherited in an autosomal recessive manner, **malignant hyperthermia** is characteristically autosomal dominant. - Autosomal recessive disorders typically require two copies of the mutated gene (one from each parent) to manifest, which is not the primary inheritance pattern for this condition. *X linked recessive* - **X-linked recessive** inheritance primarily affects males, with females usually being carriers, and is not the typical mode of inheritance for **malignant hyperthermia**. - Conditions like Duchenne muscular dystrophy exemplify X-linked recessive inheritance. *X linked dominant* - **X-linked dominant** disorders affect both males and females, but often with differing severity or presentation, and are not the characteristic inheritance pattern for **malignant hyperthermia**. - While rare, X-linked dominant conditions like Rett syndrome have distinct inheritance patterns.

Q: Which one of the following statements is false regarding chronic granulomatous disease?

It is an autosomal dominant disease. ### It is an autosomal dominant disease - The most common and severe form of chronic granulomatous disease (CGD) is inherited as an **X-linked recessive disorder**. - There are also autosomal recessive forms, but **never autosomal dominant inheritance**. *Recurrent staphylococcal infections are usual in this disease* - Patients with CGD are particularly susceptible to infections with **catalase-positive organisms** like *Staphylococcus aureus* because their phagocytes cannot effectively kill these microbes. - This is due to a defect in the **NADPH oxidase enzyme**, which impairs the production of reactive oxygen species essential for bacterial killing [1]. *Nitro blue tetrazolium test is useful for screening* - The **nitroblue tetrazolium (NBT) test** is a traditional screening method for CGD, as it detects the ability of phagocytes to produce a **respiratory burst** and reduce NBT dye [1]. - In CGD, the NBT dye remains yellow (unreduced) due to the absence or deficiency of NADPH oxidase activity. *It is characterized by abnormal bacterial phagocytosis* - CGD is characterized by **defective intracellular killing of phagocytosed bacteria and fungi**, not abnormal phagocytosis itself. - Phagocytes (neutrophils, macrophages) can engulf microbes normally, but they fail to produce the **oxidative burst** necessary to destroy them [1].

Q: Which one of the following is NOT a contraindication in Porphyria?

High calorie diet. ***High calorie diet*** - A **high caloric intake**, especially with **carbohydrates**, is often used as a treatment strategy for acute porphyric attacks. This approach helps to suppress **ALAS1 activity**, thereby reducing the synthesis of porphyrin precursors that accumulate in porphyria. - Maintaining adequate nutrition is beneficial in general and does not exacerbate porphyria; rather, **fasting** and **starvation** can precipitate acute attacks by increasing **heme synthesis** and porphyrin precursor production [1]. *Alcohol* - Alcohol is a well-known **precipitating factor** for acute porphyria attacks [1]. It induces **hepatic cytochrome P450 enzymes**, which in turn stimulate **ALAS1 activity**—the rate-limiting enzyme in heme synthesis, leading to an overproduction of porphyrin precursors [2]. - Its metabolism can also deplete **hepatic glucose stores**, contributing to a state that mimics starvation, further exacerbating the disease. *Norethisterone* - **Norethisterone**, a synthetic progesterone, is a potent inducer of **ALAS1 activity** in the liver and is therefore contraindicated in individuals with acute intermittent porphyria (AIP) due to its ability to trigger acute attacks. - Many hormonal contraceptives and steroids can exacerbate porphyria by promoting **heme synthesis**, so they must be avoided or used with extreme caution [1]. *Phenobarbitone* - **Phenobarbitone**, a barbiturate, is a classic example of a drug that is **absolutely contraindicated** in porphyria. It potently induces **hepatic cytochrome P450 enzymes** and significantly upregulates **ALAS1 activity**, leading to a surge in neurotoxic porphyrin precursors [2]. - Its use can precipitate severe and life-threatening attacks of acute porphyria, including neurological symptoms, and should always be avoided in affected individuals.

Q: History of dislike for sweet food items is typically present in:

Hereditary fructose intolerance. ***Hereditary fructose intolerance*** - Patients with hereditary fructose intolerance develop severe symptoms like **nausea, vomiting, abdominal pain, and hypoglycemia** after ingesting fructose, leading to an aversive response and **dislike for sweet food items**. - This aversion is a protective mechanism, as avoiding fructose-containing foods (including many sweets) prevents the accumulation of toxic metabolites due to a deficiency in **hepatic aldolase B**. *Glycogen storage disease* - While glycogen storage diseases can cause hypoglycemia, they typically do not lead to a specific **aversion to sweet foods**. - The primary defect is in **glycogen synthesis or breakdown**, leading to symptoms like hepatomegaly, muscle weakness, and exercise intolerance. *Diabetes mellitus* - Patients with diabetes mellitus often have a **craving for sweet foods** due to uncontrolled blood glucose levels and insulin resistance, rather than a dislike. - The condition is characterized by **hyperglycemia** and may involve polydipsia, polyuria, and polyphagia. *Galactosemia* - Galactosemia involves an inability to metabolize galactose, leading to symptoms such as **vomiting, lethargy, and jaundice** upon milk ingestion [1]. - While patients will avoid milk, their aversion is not generally to all sweet foods, as sweet foods do not always contain galactose [1].

Q: Transplantation between identical twins-

Isograft. ***Isograft*** - An **isograft** refers to a transplant between **genetically identical individuals**, such as identical twins, thus minimizing immune rejection [1]. - Due to the identical genetic makeup, the recipient's immune system will not recognize the transplanted tissue as foreign, making **immunosuppression unnecessary** [1]. *Xenograft* - A **xenograft** involves transplantation of tissues or organs between **different species**, for example, from a pig to a human. - These grafts typically face severe and rapid **immune rejection** due to significant genetic differences between the donor and recipient species. *Autograft* - An **autograft** is a transplant of tissue from **one part of an individual's body to another part of the same individual**. - This type of graft has no risk of rejection as the tissue is genetically identical to the recipient's own tissue [2]. *Allograft* - An **allograft** is a transplant between **genetically non-identical individuals of the same species**, such as between two non-twin humans. - These grafts always require **immunosuppressive therapy** to prevent rejection due to genetic differences, though rejection rates vary based on HLA matching [1].

Q: All of the following are associated with malignancy except:

Fragile X syndrome. ***Fragile X syndrome*** - Fragile X syndrome is primarily associated with **intellectual disability** and developmental delays, not an increased risk of malignancy [1]. - It is caused by an expansion of the **CGG repeat** in the FMR1 gene, leading to reduced or absent FMRP protein. *Down syndrome* - Individuals with Down syndrome (Trisomy 21) have a significantly increased risk of developing certain cancers, particularly **acute lymphoblastic leukemia (ALL)** and **acute myeloid leukemia (AML)**. - This increased leukemia risk is several times higher than in the general population. *Fanconi anemia* - Fanconi anemia is a rare genetic disorder characterized by **bone marrow failure** and an increased predisposition to various cancers. - Patients are at a higher risk for **acute myeloid leukemia (AML)** and **myelodysplastic syndromes (MDS)**, as well as head and neck squamous cell carcinomas. *Bloom syndrome* - Bloom syndrome is a very rare genetic disorder associated with an exceptionally high risk of developing a wide range of cancers early in life. - This increased susceptibility is due to **genomic instability** and a high frequency of chromosomal rearrangements.

Q: A 60-year-old man presents with choreoathetosis. On examination, Kayser-Fleischer rings are seen in the cornea. What is the initial treatment of choice for this condition?

Zinc (reduces copper absorption). ***Zinc (reduces copper absorption)*** - **Zinc** is often the initial treatment of choice, especially in asymptomatic or mildly symptomatic patients, as it works by inducing **metallothionein** in the intestinal cells, which binds copper and prevents its absorption. - This reduces the body's copper load without causing potential side effects associated with intense chelation, making it a safer first-line option. *Penicillamine (a chelating agent)* - **D-penicillamine** is a chelating agent that binds to copper and promotes its excretion; however, it has significant side effects such as **nephrotoxicity** and **bone marrow suppression**. - Its use is generally reserved for patients who cannot tolerate zinc or require more aggressive copper removal. *Trientine (a chelating agent)* - **Trientine** is another copper chelating agent, often preferred over penicillamine due to its better side-effect profile but still considered a more aggressive treatment than zinc. - It is typically used for patients who are unable to tolerate penicillamine or require chelation. *Pyridoxine (Vitamin B6)* - **Pyridoxine (Vitamin B6)** is not a direct treatment for Wilson's disease. - It's mainly used to prevent or treat peripheral neuropathy in patients receiving **isoniazid** or **penicillamine**, as penicillamine can sometimes interfere with B6 metabolism [1].

Q: Which of the following is autosomal dominant in inheritance?

Achondroplasia. ***Achondroplasia*** - This condition is inherited in an **autosomal dominant** pattern, meaning only one copy of the mutated gene is needed to cause the disorder. - It is caused by a mutation in the **FGFR3 gene**, leading to abnormal bone growth and short-limbed dwarfism [1]. *Hemochromatosis* - This condition is primarily inherited in an **autosomal recessive** pattern, meaning two copies of the mutated gene (HFE gene) are required for the disease to manifest. - It leads to excessive iron absorption and organ damage. *Sickle cell disease* - This is an **autosomal recessive** disordertoo. - It results from a mutation in the **HBB gene**, affecting hemoglobin and causing red blood cells to become sickle-shaped. *Wiskott Aldrich syndrome* - This is an **X-linked recessive** disorder, meaning it primarily affects males. - It involves mutations in the **WAS gene**, leading to immunodeficiency, eczema, and thrombocytopenia.

Q: Which of the following disorders presents with repeated catalase positive infections?

CGD. ***CGD*** - Chronic Granulomatous Disease (CGD) is characterized by a defect in **NADPH oxidase**, preventing phagocytes from producing a **respiratory burst** to kill certain bacteria and fungi. - Patients with CGD are particularly susceptible to infections by **catalase-positive organisms** because these organisms degrade hydrogen peroxide, which CGD phagocytes rely on for killing. *Chediak higashi syndrome* - This syndrome involves defective lysosomal trafficking, leading to impaired neutrophil chemotaxis and degranulation, resulting in recurrent infections, but not specifically to **catalase-positive organisms**. - Other features include **partial albinism**, peripheral neuropathy, and normal respiratory burst. *SCID* - Severe Combined Immunodeficiency (SCID) involves a profound defect in both **T-cell and B-cell immunity**, leading to severe and recurrent infections by a wide range of pathogens, not limited to catalase-positive ones [1]. - Patients typically present in infancy with **failure to thrive**, opportunistic infections, and lack of lymphoid tissue [1]. *X linked hypogammaglobulinemia* - Also known as **Bruton's agammaglobulinemia**, this disorder involves a defect in B-cell maturation, leading to the absence of antibodies and recurrent bacterial infections [1]. - The infections are typically with **encapsulated bacteria** and are not specifically linked to catalase-positive organisms [1].

Question 1

Not true about blue sclera

Accepted Answer

Seen in Marfan's syndrome

Answer

Blue colour is produced by underlying uveal pigment

Answer

Seen in osteogenesis imperfecta

Answer

Not seen in Ehlers-Danlos syndrome

Question 2

A patient taken for surgery was given suxamethonium, following which his body temperature began to rise quickly. Along with this he also developed masseter spasm, tachycardia and arrhythmia. An ABG analysis also revealed that he has hypoxia, hypercarbia and acidosis. What is the mode of inheritance of the condition described above?

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X linked recessive

Answer

X linked dominant

Question 3

Which one of the following statements is false regarding chronic granulomatous disease?

Accepted Answer

It is an autosomal dominant disease

Answer

Recurrent staphylococcal infections are usual in this disease

Answer

Nitro blue tetrazolium test is useful for screening

Answer

It is characterized by abnormal bacterial phagocytosis

Question 4

Which one of the following is NOT a contraindication in Porphyria?

Accepted Answer

High calorie diet

Answer

Alcohol

Answer

Norethisterone

Answer

Phenobarbitone

Question 5

History of dislike for sweet food items is typically present in:

Accepted Answer

Hereditary fructose intolerance

Answer

Glycogen storage disease

Answer

Diabetes mellitus

Answer

Galactosemia

Question 6

Transplantation between identical twins-

Accepted Answer

Isograft

Answer

Xenograft

Answer

Autograft

Answer

Allograft

Question 7

All of the following are associated with malignancy except:

Accepted Answer

Fragile X syndrome

Answer

Down syndrome

Answer

Fanconi anemia

Answer

Bloom syndrome

Question 8

A 60-year-old man presents with choreoathetosis. On examination, Kayser-Fleischer rings are seen in the cornea. What is the initial treatment of choice for this condition?

Accepted Answer

Zinc (reduces copper absorption)

Answer

Penicillamine (a chelating agent)

Answer

Trientine (a chelating agent)

Answer

Pyridoxine (Vitamin B6)

Question 9

Which of the following is autosomal dominant in inheritance?

Accepted Answer

Achondroplasia

Answer

Hemochromatosis

Answer

Sickle cell disease

Answer

Wiskott Aldrich syndrome

Question 10

Which of the following disorders presents with repeated catalase positive infections?

Accepted Answer

CGD

Answer

Chediak higashi syndrome

Answer

SCID

Answer

X linked hypogammaglobulinemia

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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