Genetic Disorders and Biochemical Pathology Practice Questions

Q: Dystrophic gene mutation leads to which of the following conditions?

Duchenne muscular dystrophy. **Explanation:** **Duchenne Muscular Dystrophy (DMD)** is caused by a mutation in the **DMD gene**, located on the short arm of the **X chromosome (Xp21)**. This gene is the largest known human gene, making it highly susceptible to spontaneous mutations. It encodes **dystrophin**, a critical cytoplasmic protein that links the intracellular actin cytoskeleton of the muscle fiber to the extracellular matrix via the dystroglycan complex. In DMD, a "frameshift" mutation leads to a near-complete absence of dystrophin, resulting in membrane instability, calcium influx, and progressive myofiber necrosis. **Analysis of Incorrect Options:** * **Myasthenia Gravis:** An autoimmune channelopathy caused by antibodies against the **postsynaptic acetylcholine receptors (AChR)** at the neuromuscular junction, not a genetic mutation of structural proteins. * **Motor Neuron Disease (MND):** A neurodegenerative disorder affecting upper and lower motor neurons. While some forms (like ALS) have genetic links (e.g., SOD1 mutation), it is not related to the dystrophin gene. * **Poliomyelitis:** An infectious disease caused by the **Poliovirus**, which selectively destroys the anterior horn cells of the spinal cord. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** X-linked recessive (primarily affects males). * **Becker Muscular Dystrophy (BMD):** Also involves the DMD gene but results from "in-frame" mutations, leading to truncated but partially functional dystrophin (milder phenotype). * **Clinical Signs:** Gower’s sign (using hands to "climb up" the body to stand) and pseudohypertrophy of calves (fatty replacement of muscle). * **Biochemical Marker:** Significantly elevated **Creatine Kinase (CK-MM)** levels are seen even in the preclinical stage. * **Death:** Usually occurs due to respiratory failure or dilated cardiomyopathy.

Q: In Wilson disease, which element is chelated?

Zinc. **Explanation:** In the context of **Wilson Disease** (Hepatolenticular degeneration), the question asks which element is **chelated** as a therapeutic intervention. While Wilson disease is a disorder of **copper** metabolism, the correct answer is **Zinc** because it acts as a pharmacological chelator/antagonist used in long-term maintenance therapy. **Why Zinc is Correct:** Zinc (usually as Zinc Acetate) induces the synthesis of **Metallothionein** in the intestinal mucosal cells. Metallothionein is an endogenous chelator that has a high affinity for copper. It binds dietary copper within the enterocytes, preventing its absorption into the portal circulation. The bound copper is then excreted safely in the feces as the intestinal cells are sloughed off. **Analysis of Incorrect Options:** * **Option A (Iron):** Iron chelation (e.g., Deferoxamine) is used in Hemochromatosis or Thalassemia, not Wilson disease. * **Option C (Copper):** Copper is the element that *accumulates* pathologically due to a mutation in the **ATP7B gene**. While drugs like D-Penicillamine and Trientine are used to chelate and excrete copper via urine, Zinc is the specific element among the options that functions as an indirect chelator/blocker of absorption. * **Option D (Selenium):** Selenium is a cofactor for Glutathione Peroxidase and has no role in the chelation therapy of Wilson disease. **NEET-PG High-Yield Pearls:** * **Gold Standard Diagnosis:** Liver biopsy (increased hepatic copper >250 μg/g dry weight). * **Screening:** Low serum Ceruloplasmin and presence of **Kayser-Fleischer (KF) rings** on slit-lamp exam. * **Treatment Triad:** 1. **D-Penicillamine:** First-line chelator (Side effect: Nephrotic syndrome, B6 deficiency). 2. **Trientine:** Preferred if Penicillamine is not tolerated. 3. **Zinc:** Best for maintenance and asymptomatic patients.

Q: Which of the following is an autosomal dominant metabolic disorder?

Familial hypercholesterolemia. **Explanation:** The correct answer is **Familial Hypercholesterolemia (FH)**. **1. Why Familial Hypercholesterolemia is correct:** Most metabolic disorders (enzymopathies) follow an autosomal recessive (AR) inheritance pattern because a 50% reduction in enzyme activity in heterozygotes is usually sufficient for normal function. However, **Familial Hypercholesterolemia** is a notable exception. It is an **Autosomal Dominant (AD)** disorder caused by mutations in the **LDL receptor gene**. This leads to a "dosage effect" where even a 50% reduction in functional receptors (heterozygotes) causes significant elevation in plasma LDL, leading to premature atherosclerosis and xanthomas. **2. Why other options are incorrect:** * **Cystic Fibrosis:** This is the most common lethal **Autosomal Recessive** disorder in Caucasians, caused by a mutation in the CFTR gene on Chromosome 7. * **Phenylketonuria (PKU):** This is a classic **Autosomal Recessive** metabolic disorder caused by a deficiency of Phenylalanine Hydroxylase. * **Alpha-1-antitrypsin deficiency:** This follows an **Autosomal Recessive** (specifically co-dominant) inheritance pattern, leading to emphysema and liver cirrhosis. **3. NEET-PG Clinical Pearls:** * **Mnemonic for AD Metabolic Disorders:** Most AD disorders are structural (e.g., Marfan) or regulatory. Metabolic exceptions include **FH**, **Acute Intermittent Porphyria (AIP)**, and **Hereditary Spherocytosis**. * **FH Clinical Markers:** Look for **Tendon Xanthomas** (especially Achilles) and **Corneal Arcus** in a young patient with a family history of early Myocardial Infarction. * **Genetics:** Homozygous FH is much more severe, often presenting with MI before age 20.

Q: Which of the following diseases has an autosomal recessive inheritance pattern?

Cystic fibrosis. **Explanation:** **Cystic Fibrosis (Option A)** is the correct answer. It is one of the most common **autosomal recessive** disorders, particularly in Caucasian populations. It is caused by a mutation in the **CFTR gene** located on **chromosome 7**. This mutation leads to defective chloride ion transport across epithelial membranes, resulting in thick, dehydrated secretions in the lungs, pancreas, and reproductive tract. **Analysis of Incorrect Options:** * **Hydrocephalus (Option B):** This is a clinical sign (excess CSF accumulation) rather than a single genetic disease. While it can be part of genetic syndromes, the most common inherited form (X-linked aqueductal stenosis) follows an **X-linked recessive** pattern. Most cases are sporadic or acquired (e.g., post-meningitic). * **Duchenne Muscular Dystrophy (Option C):** This is a classic example of an **X-linked recessive** disorder. It involves a mutation in the *Dystrophin* gene (the largest known human gene), primarily affecting males. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Autosomal Recessive (AR) Disorders:** "ABCDE PQRST" – **A**lbinism, **B**artter syndrome, **C**ystic fibrosis/CAH, **D**eafness (sensorineural), **E**nzyme deficiencies (most), **P**KU, **Q**-fever (not genetic, but used for flow), **R**enal tubular acidosis, **S**ickle cell anemia/Thalassemia, **T**ay-Sachs. * **CFTR Mutation:** The most common mutation is **ΔF508** (deletion of phenylalanine at position 508). * **Diagnostic Gold Standard:** Sweat Chloride Test (Chloride levels >60 mmol/L). * **Associated Finding:** Congenital Bilateral Absence of the Vas Deferens (CBAVD) leading to infertility in males.

Q: Bronze diabetes is seen in which of the following conditions?

Hemochromatosis. **Explanation:** **Bronze Diabetes** is the classic clinical triad of **hyperpigmentation, diabetes mellitus, and cirrhosis**, specifically associated with **Hereditary Hemochromatosis**. 1. **Why Hemochromatosis is correct:** Hemochromatosis is an autosomal recessive disorder (most commonly a mutation in the **HFE gene**) leading to excessive intestinal iron absorption. The excess iron is deposited as **hemosiderin** in various organs. * **Skin:** Iron deposition and increased melanin production cause a "bronze" metallic tint. * **Pancreas:** Iron deposition in the islets of Langerhans causes selective destruction of beta cells, leading to secondary diabetes mellitus. * **Liver:** Leads to micronodular cirrhosis and increases the risk of Hepatocellular Carcinoma (HCC). 2. **Why other options are incorrect:** * **Wilson’s Disease:** A disorder of copper metabolism. While it affects the liver and brain (basal ganglia), it typically presents with Kayser-Fleischer (KF) rings and neurological symptoms, not bronze skin or diabetes. * **Sarcoidosis:** A granulomatous disease that can affect the pancreas, but it is a rare cause of diabetes and does not cause the characteristic bronze pigmentation. * **Lead Intoxication:** Presents with abdominal pain (colic), peripheral neuropathy (wrist drop), and "Burtonian lines" on gums, but does not involve iron-related skin or pancreatic pathology. **High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard Diagnosis:** Liver biopsy with **Prussian Blue staining** (to quantify the Hepatic Iron Index). * **Screening Test of Choice:** Transferrin saturation (increased) and Serum Ferritin. * **Treatment:** Therapeutic phlebotomy is the mainstay; iron chelators (e.g., Deferoxamine) are used if phlebotomy is contraindicated. * **Other associations:** Dilated cardiomyopathy and "Pseudogout" (Calcium pyrophosphate deposition).

Q: Which cell organelle is affected in Wolman’s Disease?

Lysosome. **Explanation:** **Wolman’s Disease** is a severe, autosomal recessive **Lysosomal Storage Disorder (LSD)**. It is caused by a deficiency of the enzyme **Lysosomal Acid Lipase (LAL)**. Under normal physiological conditions, this enzyme is responsible for hydrolyzing cholesteryl esters and triglycerides within the **lysosome**. In its absence, these lipids accumulate massively in the lysosomes of various tissues (liver, spleen, and adrenal glands), leading to multi-organ failure. **Analysis of Options:** * **Option B (Lysosome):** This is the correct site of pathology. The LAL enzyme deficiency leads to the entrapment of lipids inside the lysosomal compartment, characterizing it as a classic LSD. * **Option A (Peroxisome):** Peroxisomes are involved in long-chain fatty acid oxidation (beta-oxidation). Disorders related to peroxisomes include Zellweger Syndrome and Adrenoleukodystrophy, not Wolman’s. * **Option C (Liposome):** Liposomes are artificial spherical vesicles used primarily for drug delivery; they are not naturally occurring functional organelles involved in this disease pathology. * **Option D (Dictyosome):** This is another term for the stacks of the Golgi apparatus, which is involved in protein packaging and modification, not the primary site of lipid hydrolysis. **High-Yield Clinical Pearls for NEET-PG:** * **Pathognomonic Sign:** Bilateral **adrenal calcification** is a classic radiological finding in Wolman’s Disease. * **Clinical Presentation:** Hepatomegaly, splenomegaly, steatorrhea, and failure to thrive in infancy. * **Spectrum:** **Cholesteryl Ester Storage Disease (CESD)** is a milder, later-onset form of LAL deficiency compared to the infantile-onset Wolman’s Disease. * **Treatment:** Enzyme replacement therapy (Sebelipase alfa) is now available.

Q: Wilson disease is due to the accumulation of which element?

Copper. **Explanation:** **Wilson Disease (Hepatolenticular Degeneration)** is an autosomal recessive disorder caused by a mutation in the **ATP7B gene** located on chromosome 13. This gene encodes a copper-transporting P-type ATPase. **1. Why Copper is Correct:** In a healthy individual, ATP7B is responsible for incorporating copper into apoceruloplasmin to form **ceruloplasmin** and facilitating the excretion of excess copper into the bile. In Wilson disease, this mechanism fails, leading to the toxic accumulation of **Copper** in various tissues, primarily the **liver** (cirrhosis), **brain** (basal ganglia/lenticular nucleus degeneration), and the **cornea** (Kayser-Fleischer rings). **2. Why Other Options are Incorrect:** * **Iron:** Accumulation of iron leads to **Hemochromatosis**, characterized by the "bronze diabetes" triad (pigmentation, diabetes, and cirrhosis). * **Zinc:** Zinc is actually used as a **treatment** for Wilson disease because it induces metallothionein in intestinal cells, which sequesters copper and prevents its absorption. * **Nickel:** While nickel can be toxic in industrial settings, it is not associated with a specific primary genetic storage disorder like Wilson disease. **3. High-Yield Clinical Pearls for NEET-PG:** * **Diagnosis:** Low serum ceruloplasmin, increased urinary copper excretion, and increased hepatic copper content (Gold Standard). * **Ocular Sign:** **Kayser-Fleischer (KF) rings** (copper deposition in the Descemet’s membrane). * **Neurological Sign:** "Giant Panda Face" appearance on MRI of the midbrain. * **Treatment:** Chelating agents like **D-Penicillamine** or Trientine, and Zinc for maintenance.

Question 1

Dystrophic gene mutation leads to which of the following conditions?

Accepted Answer

Duchenne muscular dystrophy

Answer

Myasthenia gravis

Answer

Motor neuron disease

Answer

Poliomyelitis

Question 2

What conditions may develop in a child born to a mother with phenylketonuria?

Accepted Answer

Microcephaly, mental retardation, congenital heart disease

Answer

Mental retardation, cataract, congenital heart disease

Answer

Hydrocephalus, cataract

Answer

Microcephaly, cataract, renal dysplasia

Question 3

In Wilson disease, which element is chelated?

Accepted Answer

Zinc

Answer

Iron

Answer

Copper

Answer

Selenium

Question 4

Which of the following is an autosomal dominant metabolic disorder?

Accepted Answer

Familial hypercholesterolemia

Answer

Cystic fibrosis

Answer

Phenylketonuria

Answer

Alpha-1-antitrypsin deficiency

Question 5

Which of the following diseases has an autosomal recessive inheritance pattern?

Accepted Answer

Cystic fibrosis

Answer

Hydrocephalus

Answer

Duchene muscular dystrophy

Answer

None of the above

Question 6

Adrenogenital syndrome is most commonly caused by which of the following?

Accepted Answer

21-hydroxylase deficiency

Answer

17-alpha-hydroxylase deficiency

Answer

3-beta-hydroxylase deficiency

Answer

Steroid sulfatase deficiency

Question 7

Bronze diabetes is seen in which of the following conditions?

Accepted Answer

Hemochromatosis

Answer

Wilson's disease

Answer

Sarcoidosis

Answer

Lead intoxication

Question 8

Which cell organelle is affected in Wolman’s Disease?

Accepted Answer

Lysosome

Answer

Peroxisome

Answer

Liposome

Answer

Dictyosome

Question 9

A 2-month-old infant presents with failure to thrive, recurrent emesis, hepatosplenomegaly, and adrenal insufficiency. Adrenal calcification is noted radiologically. What is the most likely diagnosis?

Accepted Answer

Wolman's disease

Answer

Adrenal hemorrhage

Answer

Pheochromocytoma

Answer

Addison's disease

Question 10

Wilson disease is due to the accumulation of which element?

Accepted Answer

Copper

Answer

Iron

Answer

Zinc

Answer

Nickel

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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