Genetic Disorders and Biochemical Pathology Practice Questions

Q: An affected male infant born to unaffected parents could be an example of all of the following inheritance patterns, except?

Autosomal dominant disorder. In genetics, the inheritance pattern is determined by how a trait or disorder is passed from parents to offspring. **Explanation of the Correct Answer (A):** In an **Autosomal Dominant (AD)** disorder, the presence of a single mutant allele is sufficient to cause the disease [1]. Typically, an affected individual must have at least one affected parent (vertical transmission). If both parents are phenotypically unaffected, they do not carry the dominant allele; therefore, they cannot pass it to their offspring. *Note: While "de novo" mutations can occur, in the context of standard Mendelian inheritance patterns used in exams, an affected child from unaffected parents is the classic "rule-out" for AD inheritance.* **Explanation of Incorrect Options:** * **B. Autosomal Recessive (AR):** This is the classic scenario for AR disorders. Both parents are asymptomatic **carriers** (heterozygous) [1]. There is a 25% chance for each pregnancy to result in an affected child (homozygous recessive). * **C. Polygenic Disorder:** These result from the cumulative effect of multiple genes and environmental factors (e.g., cleft lip, neural tube defects). Parents often do not show the full phenotype but carry a "threshold" of genetic liability. * **D. Sex-linked Recessive (XLR):** In XLR disorders (e.g., Hemophilia), an unaffected mother can be a carrier. She can pass the mutant X chromosome to her son, who will be affected because he is hemizygous. **High-Yield Clinical Pearls for NEET-PG:** * **Horizontal Transmission:** Characteristic of Autosomal Recessive (seen in siblings). * **Vertical Transmission:** Characteristic of Autosomal Dominant (seen in every generation). * **Father-to-Son Transmission:** Never occurs in X-linked inheritance. * **Consanguinity:** Significantly increases the risk of Autosomal Recessive disorders.

Q: Which of the following is NOT a lysosomal storage disorder?

McArdle's disease. **Explanation:** The correct answer is **McArdle’s disease** because it is a **Glycogen Storage Disorder (GSD Type V)**, not a lysosomal storage disorder. It is caused by a deficiency of **muscle glycogen phosphorylase (myophosphorylase)**, an enzyme located in the cytosol, not the lysosome. This leads to an inability to break down muscle glycogen during exercise, resulting in exercise intolerance, muscle cramps, and myoglobinuria. **Analysis of other options:** * **I-cell disease (Mucolipidosis II):** A lysosomal disorder caused by a deficiency in **N-acetylglucosaminyl-1-phosphotransferase**. This leads to the failure of tagging enzymes with Mannose-6-Phosphate, causing lysosomal enzymes to be secreted extracellularly rather than being delivered to the lysosome. * **Hunter’s disease (MPS II):** A lysosomal storage disorder (Mucopolysaccharidosis) caused by a deficiency of **Iduronate-2-sulfatase**, leading to the accumulation of heparan and dermatan sulfate. * **Farber’s disease:** A rare lysosomal storage disorder caused by a deficiency of **acid ceramidase**, leading to the accumulation of ceramide in lysosomes. **High-Yield Clinical Pearls for NEET-PG:** * **McArdle’s Hallmark:** "Second wind" phenomenon and a flat lactate curve during an ischemic exercise test. * **Hunter vs. Hurler:** Hunter’s is **X-linked Recessive** and lacks corneal clouding (mnemonic: *"The Hunter needs clear eyes to see the target"*). * **I-Cell Disease:** Characterized by coarse facial features, skeletal abnormalities, and massive amounts of lysosomal enzymes found in the **serum**.

Q: Which type of inheritance is indicated?

Mitochondrial inheritance. ***Mitochondrial inheritance*** - Shows **maternal transmission** pattern where all offspring of affected mothers inherit the condition, regardless of sex. - **Affected fathers do not transmit** the trait to their children, as mitochondria are inherited exclusively from the mother. *Autosomal recessive* - Requires **both parents to be carriers** for affected offspring, typically showing a **25% recurrence risk** in each pregnancy. - Would show **horizontal pattern** affecting siblings but not necessarily all children of affected mothers. *Autosomal dominant* - Shows **vertical transmission** with **50% risk** to each offspring from an affected parent, regardless of parent's sex. - **Affected fathers would transmit** the condition to approximately half their children, which contradicts the maternal-only pattern. *X-linked recessive* - Primarily affects **males** with carrier mothers showing **50% risk** for affected sons and carrier daughters. - Would show **skewed sex distribution** favoring males and **no male-to-male transmission**, not equal sex involvement.

Q: The gene for Wilson's disease is located on which chromosome?

Long arm of Chromosome 13. **Explanation:** **Wilson’s Disease (Hepatolenticular Degeneration)** is an autosomal recessive disorder of copper metabolism. The correct answer is **Option A (Long arm of Chromosome 13)** because the disease is caused by a mutation in the **ATP7B gene**, which is located on chromosome **13q14.3**. This gene encodes a P-type ATPase copper-transporting protein responsible for transporting copper into the bile and incorporating it into apoceruloplasmin to form ceruloplasmin. A defect leads to toxic copper accumulation in the liver, brain (basal ganglia), and cornea. **Analysis of Incorrect Options:** * **Option B & D (Chromosome 6):** Chromosome 6 is the site of the **HFE gene** (specifically 6p21.3), which is mutated in **Hereditary Hemochromatosis** (iron overload). * **Option C (Short arm of Chromosome 13):** The ATP7B gene is specifically located on the **long arm (q)**, not the short arm (p). In genetics, "q" stands for the long arm (queue) and "p" for the short arm (petit). **High-Yield Clinical Pearls for NEET-PG:** * **Biochemical Markers:** Low serum ceruloplasmin, increased urinary copper excretion, and increased hepatic copper content. * **Ocular Sign:** **Kayser-Fleischer (KF) rings** due to copper deposition in the Descemet’s membrane of the cornea. * **Neurological Sign:** "Wing-beating" tremor and parkinsonian features. * **Diagnosis:** Liver biopsy is the gold standard; "Giant Panda" sign on MRI brain. * **Treatment:** Copper chelators like **D-Penicillamine** (first-line) or Trientine, and Zinc (to prevent absorption).

Q: Which chromosome is associated with cystic fibrosis?

7. **Explanation:** **1. Correct Answer: Option A (Chromosome 7)** Cystic Fibrosis (CF) is an **autosomal recessive** multisystem disorder caused by mutations in the **CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene**, which is located on the **long arm (q) of Chromosome 7** (specifically at position 7q31.2). The CFTR protein functions as a cAMP-regulated chloride channel. The most common mutation is the **ΔF508** (deletion of phenylalanine at position 508), which leads to protein misfolding and degradation in the endoplasmic reticulum. **2. Analysis of Incorrect Options:** * **Option B (Chromosome 8):** Associated with conditions like **Hereditary Spherocytosis** (ANK1 gene) and Myc oncogene translocations (Burkitt Lymphoma). * **Option C (Chromosome 11):** A high-yield chromosome containing genes for **Beta-globin** (Sickle cell anemia, Beta-thalassemia), Insulin, and the WT1 gene (Wilms tumor). * **Option D (Chromosome 13):** Associated with **Patau Syndrome** (Trisomy 13), **Wilson disease** (ATP7B gene), and **Retinoblastoma** (RB1 gene). **3. Clinical Pearls for NEET-PG:** * **Diagnosis:** The gold standard is the **Pilocarpine Iontophoresis Sweat Chloride Test** (Chloride >60 mEq/L is diagnostic). * **Clinical Presentation:** Recurrent pulmonary infections (*Pseudomonas* is common), pancreatic insufficiency (steatorrhea), and **meconium ileus** in newborns. * **Infertility:** 95% of males are infertile due to **Congenital Bilateral Absence of Vas Deferens (CBAVD)**. * **Biochemical Hallmark:** Defective chloride transport leads to thick, dehydrated secretions in the lungs and pancreas.

Q: An infant is unable to feed properly, is weak, and not gaining weight. The mother reports multiple episodes of urination with crying each time the baby passes urine. She also notes that the baby often smells of rotten fish in his urine and sweat. Which of the following would you test for in the infant's urine?

Trimethylamine. ### Explanation **Correct Option: C. Trimethylamine** The clinical presentation of a "rotten fish" odor in the urine and sweat is the pathognomonic sign of **Trimethylaminuria**, also known as **Fish Odor Syndrome**. This condition is caused by a deficiency of the enzyme **Flavin-containing monooxygenase 3 (FMO3)**. Normally, FMO3 converts trimethylamine (TMA)—a malodorous byproduct of bacterial degradation of choline, lecithin, and carnitine in the gut—into the odorless **trimethylamine N-oxide (TMAO)**. When FMO3 is deficient, TMA accumulates and is excreted through sweat, urine, and breath, resulting in the characteristic fishy smell. The infant’s failure to thrive and distress during urination (likely due to skin irritation or systemic malaise) are consistent with severe metabolic presentations. **Analysis of Incorrect Options:** * **A. Vinylmandelic acid (VMA):** This is a urinary metabolite of catecholamines (epinephrine/norepinephrine). It is used to diagnose **Neuroblastoma** in children or Pheochromocytoma in adults, but it does not cause a fishy odor. * **B. Isovaleric acid:** This accumulates in **Isovaleric Acidemia**. While it causes a distinct odor, it is described as **"sweaty feet"** or "cheesy" rather than rotten fish. * **D. Oxoisocaproic acid:** This is a branched-chain keto acid that accumulates in **Maple Syrup Urine Disease (MSUD)**. The characteristic odor associated with this is **burnt sugar** or maple syrup. **High-Yield Clinical Pearls for NEET-PG:** * **Trimethylaminuria (FMO3 deficiency):** Autosomal recessive; management involves dietary restriction of precursors (fish, eggs, legumes). * **Odor Associations:** * **Mousy/Musty:** Phenylketonuria (PKU). * **Cabbage-like/Rancid butter:** Tyrosinemia Type I. * **Sweaty feet:** Isovaleric acidemia or Glutaric aciduria type II. * **Swimming pool odor:** Hawkinsinuria.

Q: A 9-month-old infant presented with recurrent infections. Investigations revealed a near absence of B and T cells and a significantly diminished thymic shadow on chest X-ray. Which of the following metabolites would be elevated in this patient?

Deoxyadenosine. ### Explanation The clinical presentation of recurrent infections, near absence of both B and T cells (lymphopenia), and a diminished thymic shadow in a 9-month-old infant is characteristic of **Severe Combined Immunodeficiency (SCID)**. Approximately 15% of SCID cases are caused by a deficiency in the enzyme **Adenosine Deaminase (ADA)**. **Why Deoxyadenosine is Correct:** Adenosine Deaminase is a crucial enzyme in the purine salvage pathway that converts adenosine to inosine and deoxyadenosine to deoxyinosine. In ADA deficiency, **deoxyadenosine** accumulates and is phosphorylated into **dATP (deoxyadenosine triphosphate)**. High levels of dATP are toxic to lymphocytes because they inhibit **Ribonucleotide Reductase**, the enzyme responsible for DNA synthesis. This leads to a failure of T and B cell proliferation, resulting in the SCID phenotype. **Analysis of Incorrect Options:** * **A. Uric Acid:** This is the end product of purine catabolism. In ADA deficiency, the pathway is blocked upstream, typically leading to *decreased* uric acid production. * **B. Orotic Acid:** Elevated in Urea Cycle disorders (like OTC deficiency) or Orotic Aciduria. It is not directly linked to the purine salvage pathway or SCID. * **D. NADPH:** This is a cofactor produced in the HMP shunt. While essential for respiratory burst in neutrophils (deficient in Chronic Granulomatous Disease), it does not accumulate in ADA deficiency. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** ADA deficiency is the most common **Autosomal Recessive** cause of SCID (X-linked SCID is the overall most common type). * **First-line Treatment:** Bone marrow transplantation or Enzyme Replacement Therapy (PEG-ADA). * **Gene Therapy:** ADA deficiency was the first genetic disease for which gene therapy was attempted. * **Radiology:** A "missing thymic shadow" in a pediatric chest X-ray should immediately raise suspicion for SCID or DiGeorge Syndrome.

Question 1

An affected male infant born to unaffected parents could be an example of all of the following inheritance patterns, except?

Accepted Answer

Autosomal dominant disorder

Answer

Autosomal recessive disorder

Answer

Polygenic disorder

Answer

Sex-linked recessive disorder

Question 2

Which of the following is NOT a lysosomal storage disorder?

Accepted Answer

McArdle's disease

Answer

I cell disease

Answer

Hunter's disease

Answer

Farber's disease

Question 3

Which type of inheritance is indicated?

Accepted Answer

Mitochondrial inheritance

Answer

Autosomal recessive

Answer

Autosomal dominant

Answer

X-linked recessive

Question 4

Defect in which of the following proteins leads to Rett syndrome?

Accepted Answer

Methyl cytosine binding protein

Answer

Histone acetyl transferase

Answer

Ten eleven translocation

Answer

DNA methylase

Question 5

Which of the following is NOT a recognized association?

Accepted Answer

Homocystinuria and recurrent deep vein thrombosis

Answer

Abetalipoproteinemia and acanthocytosis

Answer

Refsum's disease is associated with cerebellar ataxia

Answer

Spinocerebellar ataxia in Friedreich's ataxia

Question 6

A woman who suffers from frequent and severe migraine headaches has had five children, all of whom have experienced, beginning between the ages of 8 and 12, stroke-like episodes compounded with exercise intolerance and lactic acidosis. The father of the children does not suffer from migraines, nor is he exercise intolerant. A target of a mutation that can explain these findings is most likely which one of the following?

Accepted Answer

Mitochondrial tRNA

Answer

Cytoplasmic tRNA

Answer

Cytochrome c

Answer

Pyruvate dehydrogenase

Question 7

The gene for Wilson's disease is located on which chromosome?

Accepted Answer

Long arm of Chromosome 13

Answer

Long arm of Chromosome 6

Answer

Short arm of Chromosome 13

Answer

Short arm of Chromosome 6

Question 8

Which chromosome is associated with cystic fibrosis?

Accepted Answer

7

Answer

8

Answer

11

Answer

13

Question 9

An infant is unable to feed properly, is weak, and not gaining weight. The mother reports multiple episodes of urination with crying each time the baby passes urine. She also notes that the baby often smells of rotten fish in his urine and sweat. Which of the following would you test for in the infant's urine?

Accepted Answer

Trimethylamine

Answer

Viny/mandelic acid

Answer

Isovaleric acid

Answer

Oxoisocaproic acid

Question 10

A 9-month-old infant presented with recurrent infections. Investigations revealed a near absence of B and T cells and a significantly diminished thymic shadow on chest X-ray. Which of the following metabolites would be elevated in this patient?

Accepted Answer

Deoxyadenosine

Answer

Uric acid

Answer

Orotic acid

Answer

NADPH

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

On this page

Practice by Chapter

Want unlimited practice?