Genetics and Disease Practice Questions

Q: Which of the following is a sex linked inherited disease?

G6 PD deficiency. ***G6 PD deficiency*** - **Glucose-6-phosphate dehydrogenase (G6PD) deficiency** is an **X-linked recessive** inherited disorder [1]. - Males are predominantly affected as they have only one X chromosome, and a defective gene on it will manifest the disease. *Hypogammaglobulinemia* - This is a broad term for reduced gamma globulins and can have various genetic causes, including **X-linked agammaglobulinemia (Bruton's agammaglobulinemia)**, which is indeed X-linked. However, without further specification, hypogammaglobulinemia alone doesn't definitively point to a sex-linked inheritance as other forms exist. - Other forms of hypogammaglobulinemia, such as **common variable immunodeficiency (CVID)**, can have autosomal dominant or autosomal recessive inheritance patterns or be sporadic. *Diamond-Blackfan anemia* - This is a rare **congenital hypoplastic anemia** primarily inherited in an **autosomal dominant** pattern, though some cases are sporadic. - It is caused by mutations in ribosomal protein genes, and its inheritance is not typically sex-linked. *Down syndrome* - **Down syndrome** (Trisomy 21) is a **chromosomal disorder** caused by the presence of an extra copy of chromosome 21. - It is not a sex-linked inherited disease because it involves an **autosomal chromosome**, not a sex chromosome (X or Y).

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 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: A 15 year old child has developed dystonia and poor school grades. Slit examination is shown below. Which is the initial investigation recommended for the patient ?

24 hour urinary copper. ***24 hour urinary copper*** - The image shows **Kayser-Fleischer rings**, which, combined with neurological symptoms (**dystonia, poor school grades**) in a 15-year-old, strongly indicate **Wilson's disease**. - A **24-hour urinary copper** measurement is the most reliable initial investigation to confirm the excessive copper excretion characteristic of Wilson's disease. *Serum ceruloplasmin* - While often **low** in Wilson's disease, ceruloplasmin can be normal in some patients, especially those with isolated neurological symptoms. - It's a useful screening test but **less definitive** than urinary copper excretion for diagnosis. *Serum copper* - **Total serum copper** levels can be misleading in Wilson's disease; they are often low due to decreased ceruloplasmin, but free copper is elevated. - This test alone is **not diagnostic** for Wilson's disease as it doesn't reflect the metabolically active copper. *Liver biopsy* - **Liver biopsy** is the **gold standard** for definitive diagnosis, measuring hepatic copper concentration. - However, it is an **invasive procedure** and usually reserved for cases where non-invasive tests are inconclusive or when genetic testing is unavailable.

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: A 25-year-old man presents for a routine physical examination. The patient is tall (6 ft. 5 in) and on examination he was found to have an early diastolic murmur. His family pedigree is as given below. Which of the following is the mode of inheritance by which the disease is likely to be transmitted?

Autosomal dominant. ***Autosomal dominant*** - The pedigree shows **affected individuals in every generation**, and transmission from an affected parent to approximately half of their children, which is characteristic of **autosomal dominant inheritance**. - The disease affects both males and females, and **affected fathers transmit the disease to both sons and daughters** (e.g., I-1 to II-1 and II-5), ruling out X-linked inheritance. *X linked dominant disorder* - This pattern would show affected fathers transmitting the trait to **all their daughters but no sons**, which is not seen here (e.g., father I-1 has an affected son II-1). - Also, affected mothers would transmit to half their sons and daughters, but the key discriminatory factor is the father-to-son transmission. *X-linked recessive* - X-linked recessive traits usually show **more males affected than females**, and affected sons are typically born to carrier mothers. - An affected father would **not transmit the disease to his sons**, but the pedigree clearly shows affected father I-1 transmitting to son II-1. *Autosomal recessive* - Autosomal recessive disorders typically **skip generations**, with affected individuals often born to unaffected carriers. - The pedigree shows **direct transmission** from affected parents to offspring in every generation, which is inconsistent with recessive inheritance.

Q: A 35-year-old woman presents with hepatomegaly and arthritis. Laboratory results show high serum ferritin and transferrin saturation. Which genetic defect is likely?

Hemochromatosis. ***Hemochromatosis*** - **Hepatomegaly** and **arthritis** are classic clinical manifestations of hemochromatosis, caused by **excessive iron deposition** in various organs. - **High serum ferritin** (reflecting total body iron stores) and **high transferrin saturation** (indicating increased iron absorption) are key laboratory findings for diagnosing hemochromatosis, which is predominantly caused by genetic defects in the **HFE gene** [1]. *Wilson's disease* - Characterized by impaired copper metabolism, leading to **copper accumulation** in the liver, brain, and other organs [2]. - Laboratory findings typically include **low serum ceruloplasmin** and high urinary copper excretion, rather than high ferritin and transferrin saturation [2]. *α1-antitrypsin deficiency* - This genetic disorder primarily affects the lungs (leading to **emphysema**) and liver (causing **cirrhosis** or **hepatitis**) due to a deficiency of protective α1-antitrypsin. - It would not explain the high serum ferritin or transferrin saturation, nor is arthritis a common primary symptom. *Gaucher disease* - A lysosomal storage disorder resulting from a deficiency of the **glucocerebrosidase enzyme**, leading to accumulation of **glucocerebroside** in macrophages. - Clinically presents with **hepatosplenomegaly**, bone pain, and cytopenias, but not typically with high ferritin or transferrin saturation, nor inflammatory arthritis as a primary feature.

Q: A patient with hemochromatosis experiences joint pain and fatigue. Which genetic test would confirm the diagnosis?

HFE gene mutation test. ***HFE gene mutation test*** - **Hemochromatosis** is an iron overload disorder, and the most common hereditary form is caused by mutations in the **HFE gene**. - A positive **HFE gene mutation test**, particularly for C282Y and H63D mutations, is diagnostic for hereditary hemochromatosis in patients with compatible clinical findings [1]. *BRCA1 gene test* - The **BRCA1 gene test** is used to identify mutations associated with an increased risk of developing **breast cancer** and **ovarian cancer**, not hemochromatosis [2]. - This gene is a **tumor suppressor gene** involved in DNA repair [2]. *Lynch syndrome genetic test* - **Lynch syndrome genetic testing** identifies mutations in mismatch repair genes (like MLH1, MSH2, MSH6, PMS2) that predispose individuals to various cancers, particularly **colorectal cancer** and **endometrial cancer**. - It is not related to iron metabolism or hemochromatosis. *MLH1 gene test* - The **MLH1 gene test** is a specific component of **Lynch syndrome genetic testing**, looking for mutations in the **MLH1 gene**, which is a DNA mismatch repair gene. - Mutations in MLH1 are linked to increased cancer risk, not the iron overload seen in hemochromatosis.

Q: Which genetic syndrome is associated with hundreds of colorectal polyps and almost certain progression to colorectal cancer if left untreated?

Familial adenomatous polyposis. ***Familial adenomatous polyposis*** - Characterized by the presence of **hundreds to thousands of colorectal polyps** [1], which invariably progress to **colorectal cancer** if untreated [1]. - Caused by mutations in the **APC gene** [1] and requires regular surveillance and early intervention. *Peutz-Jeghers syndrome* - Presents with **hamartomatous polyps** [1] and associated mucocutaneous pigmentations, but the polyp burden is typically much less than in familial adenomatous polyposis. - Although there is a **cancer risk** [1], it does not have the same near-certain progression to colorectal cancer as familial adenomatous polyposis. *Juvenile polyposis syndrome* - Involves multiple **juvenile polyps** [1], mostly in childhood, but they have a lower risk of cancer compared to familial adenomatous polyposis. - The associated cancer risk is not as high [1], with polyp formation typically seen as **benign**. *Lynch syndrome* - A hereditary condition associated with **non-polyposis colorectal cancer** [2] and endometrial cancer, but does not lead to numerous polyps. - Caused by mutations in **mismatch repair genes** [2] and includes a different cancer risk profile than familial adenomatous polyposis.

Question 1

Which of the following is a sex linked inherited disease?

Accepted Answer

G6 PD deficiency

Answer

Hypogamma globuinemia

Answer

Diamond blackfan disease

Answer

Down 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 is NOT a contraindication in Porphyria?

Accepted Answer

High calorie diet

Answer

Alcohol

Answer

Norethisterone

Answer

Phenobarbitone

Question 4

A 15 year old child has developed dystonia and poor school grades. Slit examination is shown below. Which is the initial investigation recommended for the patient ?

Accepted Answer

24 hour urinary copper

Answer

Serum ceruloplasmin

Answer

Serum copper

Answer

Liver biopsy

Question 5

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 6

Which of the following is autosomal dominant in inheritance?

Accepted Answer

Achondroplasia

Answer

Hemochromatosis

Answer

Sickle cell disease

Answer

Wiskott Aldrich syndrome

Question 7

A 25-year-old man presents for a routine physical examination. The patient is tall (6 ft. 5 in) and on examination he was found to have an early diastolic murmur. His family pedigree is as given below. Which of the following is the mode of inheritance by which the disease is likely to be transmitted?

Accepted Answer

Autosomal dominant

Answer

X linked dominant disorder

Answer

X-linked recessive

Answer

Autosomal recessive

Question 8

A 35-year-old woman presents with hepatomegaly and arthritis. Laboratory results show high serum ferritin and transferrin saturation. Which genetic defect is likely?

Accepted Answer

Hemochromatosis

Answer

Wilson's disease

Answer

α1-antitrypsin deficiency

Answer

Gaucher disease

Question 9

A patient with hemochromatosis experiences joint pain and fatigue. Which genetic test would confirm the diagnosis?

Accepted Answer

HFE gene mutation test

Answer

BRCA1 gene test

Answer

Lynch syndrome genetic test

Answer

MLH1 gene test

Question 10

Which genetic syndrome is associated with hundreds of colorectal polyps and almost certain progression to colorectal cancer if left untreated?

Accepted Answer

Familial adenomatous polyposis

Answer

Lynch syndrome

Answer

Peutz-Jeghers syndrome

Answer

Juvenile polyposis syndrome

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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