Genetic Disorders and Biochemical Pathology Practice Questions

Q: All of the following are autosomal dominant disorders except?

Cystic fibrosis. **Explanation:** The correct answer is **Cystic fibrosis**, which is an **Autosomal Recessive (AR)** disorder. It is caused by a mutation in the *CFTR* gene on chromosome 7, leading to defective chloride transport and thick, viscid secretions in the lungs, pancreas, and reproductive tract. **Why the other options are incorrect:** * **Tuberous sclerosis:** An **Autosomal Dominant (AD)** neurocutaneous syndrome characterized by hamartomas in multiple organs (e.g., facial angiofibromas, cortical tubers, and renal angiomyolipomas). It involves mutations in *TSC1* (hamartin) or *TSC2* (tuberin) genes. * **Polyposis coli (Familial Adenomatous Polyposis):** An **AD** condition caused by mutations in the *APC* gene on chromosome 5q. It is characterized by the development of hundreds to thousands of adenomatous colonic polyps. * **Myotonic dystrophy:** An **AD** trinucleotide repeat disorder (CTG repeat in *DMPK* gene). It is the most common adult-onset muscular dystrophy, presenting with "anticipation" and inability to relax muscles after contraction. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for AD disorders:** "**V**ery **P**owerful **M**nemonic **H**elps **A**ll **D**octors" (**V**on Willebrand/Hippel-Lindau, **P**olyposis coli, **M**yotonic dystrophy/Marfan, **H**untington/Hereditary Spherocytosis, **A**chondroplasia, **D**ystrophies/Dystonia). * **Cystic Fibrosis Key Fact:** The most common mutation is **ΔF508**. It is the most common lethal genetic disease in Caucasians. * **General Rule:** Most structural protein defects are AD, while most enzyme deficiencies are AR (exceptions exist, like Acute Intermittent Porphyria which is AD).

Q: G-6-P deficiency occurs in which of the following diseases?

Von-Gierke disease. **Explanation:** The correct answer is **Von Gierke disease (GSD Type I)**. This condition is caused by a deficiency of the enzyme **Glucose-6-Phosphatase (G-6-Pase)**, which is responsible for the final step of both glycogenolysis and gluconeogenesis: converting Glucose-6-Phosphate into free glucose. In its absence, glucose cannot be released from the liver into the bloodstream, leading to severe **fasting hypoglycemia**. The accumulated Glucose-6-Phosphate is instead shunted into alternative pathways, resulting in the "biochemical signature" of the disease: **Hyperuricemia** (via the HMP shunt), **Lactic acidosis**, and **Hyperlipidemia**. **Analysis of Incorrect Options:** * **Forbes Disease (GSD Type III):** Caused by a deficiency of the **Debranching enzyme** (α-1,6-glucosidase). It presents similarly to Von Gierke but is generally milder and characterized by the accumulation of "limit dextrins." * **Niemann-Pick Disease:** A lysosomal storage disorder caused by a deficiency of **Sphingomyelinase**, leading to the accumulation of sphingomyelin. It is characterized by hepatosplenomegaly and "foam cells" on histology. * **Tay-Sachs Disease:** A lysosomal storage disorder caused by a deficiency of **Hexosaminidase A**, leading to the accumulation of GM2 gangliosides. It presents with neurodegeneration and a cherry-red spot on the macula, but no hepatomegaly. **High-Yield Clinical Pearls for NEET-PG:** * **Von Gierke Presentation:** Doll-like facies (fatty cheeks), massive hepatomegaly, and stunted growth. * **Treatment:** Frequent oral cornstarch (slow-release glucose) and avoidance of fructose/galactose. * **GSD Type Ib:** Includes the same biochemical features as Type Ia plus **neutropenia** and recurrent infections.

Q: A child presents with hepatomegaly and hypoglycemia. There is no improvement in blood sugar even after administration of epinephrine. What is the likely diagnosis?

Von Gierke's disease. ### Explanation **1. Why Von Gierke’s Disease (Type I GSD) is the Correct Answer:** The clinical triad of **hepatomegaly**, **fasting hypoglycemia**, and **failure to respond to epinephrine** is classic for Von Gierke’s disease. This condition is caused by a deficiency of **Glucose-6-Phosphatase**, the final enzyme required for both glycogenolysis and gluconeogenesis. * **Mechanism:** Epinephrine normally stimulates glycogen breakdown into Glucose-1-Phosphate, which is then converted to Glucose-6-Phosphate (G6P). However, because the G6Pase enzyme is missing, G6P cannot be converted into free glucose to enter the bloodstream. Consequently, blood sugar levels remain low despite hormonal stimulation. **2. Why the Other Options are Incorrect:** * **Anderson’s Disease (Type IV):** Caused by a branching enzyme deficiency. It presents with cirrhosis and "limit dextrin" accumulation, but hypoglycemia is not the primary presenting feature. * **Pompe’s Disease (Type II):** Caused by lysosomal acid maltase deficiency. It primarily affects the heart (massive cardiomegaly) and muscles. Blood sugar levels are typically **normal** because cytoplasmic glycogenolysis is intact. * **McArdle’s Disease (Type V):** Caused by muscle phosphorylase deficiency. It presents with muscle cramps and myoglobinuria after exercise. It does **not** cause hypoglycemia or hepatomegaly as the liver enzyme is unaffected. **3. NEET-PG High-Yield Pearls:** * **Biochemical Hallmarks:** Look for "Hyper-LACH": **H**yperuricemia (Gout), **L**actic **A**cidosis, **C**holesterolemia (Hyperlipidemia), and **H**ypoglycemia. * **Diagnostic Clue:** If the question mentions "doll-like facies" or "protuberant abdomen," think Von Gierke’s. * **Glucagon Test:** Similar to epinephrine, administration of glucagon will fail to raise blood glucose in these patients but will significantly increase lactate levels.

Q: In Von Gierke's disease, the levels of ketone bodies are increased due to all EXCEPT:

Oxaloacetate is required for gluconeogenesis. **Explanation:** **Von Gierke’s Disease (GSD Type I)** is caused by a deficiency of **Glucose-6-Phosphatase**. This enzyme is the final common step for both glycogenolysis and gluconeogenesis. Its absence leads to severe fasting hypoglycemia. **Why Option D is the Correct Answer (The "Except"):** In Von Gierke’s disease, **gluconeogenesis is blocked** at the final step (conversion of G6P to Glucose). Because the pathway is "stalled" at the end, the body does not continue to consume oxaloacetate (OAA) for gluconeogenesis as effectively as it would in a normal fasting state. In fact, the metabolic block leads to an accumulation of glycolytic intermediates. Therefore, the statement that OAA is being depleted specifically for gluconeogenesis is incorrect in the context of this disease's pathology; rather, the ketosis is driven by the massive shift toward fatty acid oxidation due to the hormonal response to hypoglycemia. **Analysis of Incorrect Options:** * **Options A & B:** These are synonymous. The lack of G6Pase means the liver cannot release glucose into the blood, leading to profound **hypoglycemia**. * **Option C:** Low blood glucose triggers a high **Glucagon:Insulin ratio**. This stimulates hormone-sensitive lipase, leading to increased **lipolysis** and mobilization of free fatty acids (FFAs). These FFAs undergo β-oxidation in the liver, producing excess Acetyl-CoA, which is diverted into **ketogenesis**. **NEET-PG High-Yield Pearls:** * **Clinical Tetrad:** Hypoglycemia, Lactic Acidosis (due to blocked gluconeogenesis), Hyperuricemia (G6P shunted to Pentose Phosphate Pathway), and Hyperlipidemia. * **Physical Exam:** "Doll-like" facies and massive hepatomegaly (due to glycogen and lipid storage). * **Diagnostic Key:** Administration of glucagon or epinephrine **fails** to raise blood glucose but increases lactate levels.

Q: NARP syndrome is a type of:

Mitochondrial function disorder. **Explanation:** **NARP syndrome** (Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa) is a classic example of a **Mitochondrial function disorder**. It is caused by a point mutation in the **MT-ATP6 gene**, which encodes a subunit of the mitochondrial ATP synthase (Complex V). This mutation impairs the oxidative phosphorylation pathway, leading to a deficit in ATP production that primarily affects tissues with high energy demands, such as the nervous system and retina. **Why the other options are incorrect:** * **Glycogen storage disorders (GSDs):** These are caused by deficiencies in enzymes involved in glycogen synthesis or breakdown (e.g., Von Gierke or Pompe disease), primarily affecting the liver and skeletal muscles. * **Lysosomal storage disorders (LSDs):** These result from defects in lysosomal enzymes leading to the accumulation of undigested macromolecules (e.g., Gaucher or Tay-Sachs disease). * **Lipid storage disorders:** These involve the abnormal accumulation of lipids due to enzymatic defects in lipid metabolism (e.g., Niemann-Pick disease). **High-Yield Clinical Pearls for NEET-PG:** * **Maternal Inheritance:** Like most mitochondrial DNA (mtDNA) disorders, NARP is inherited exclusively from the mother. * **Heteroplasmy:** The severity of NARP depends on the ratio of mutant to wild-type mtDNA within cells. * **Leigh Syndrome Link:** If the mutation load of the MT-ATP6 gene exceeds 90%, the phenotype shifts from NARP to the more severe **Maternally Inherited Leigh Syndrome (MILS)**, characterized by infantile-onset necrotizing encephalopathy. * **Key Triad:** Always look for the combination of **Proximal neurogenic weakness, Ataxia, and Vision loss (Retinitis Pigmentosa)** in clinical vignettes.

Q: All of the following are true about Galactosemia EXCEPT?

Patients are symptomatic immediately after birth. **Explanation:** **Why Option B is the Correct Answer (The "EXCEPT"):** Classic Galactosemia (deficiency of **Galactose-1-phosphate uridyltransferase/GALT**) does not present *immediately* at birth because the fetus is protected by maternal metabolism in utero. Symptoms only manifest **after the initiation of milk feeding** (breast milk or cow’s milk formula), which contains lactose. Lactose is broken down into glucose and galactose; once galactose enters the system and cannot be metabolized, toxic metabolites begin to accumulate. Symptoms typically appear within the first few days to a week of life. **Analysis of Other Options:** * **Option A:** True. The deficiency leads to the accumulation of **Galactose-1-phosphate** (toxic to liver, kidneys, and brain) and **Galactitol** (produced via aldose reductase). Galactitol is osmotically active and is the primary cause of **cataracts**. * **Option C:** True. Accumulation of metabolites in the liver leads to hepatomegaly, jaundice (conjugated or unconjugated), and eventually cirrhosis if untreated. * **Option D:** True. There is a well-documented, high-yield association between Galactosemia and **Neonatal E. coli sepsis**. It is believed that inhibited leucocyte bactericidal activity or increased galactose levels enhance bacterial virulence. **High-Yield Clinical Pearls for NEET-PG:** * **Enzyme Deficiency:** Most common is GALT (Classic Galactosemia). * **Screening:** Reducing substances in urine (Benedict's test positive) but a negative glucose oxidase test (Dipstick). * **Clinical Triad:** Oil-drop cataracts, Liver failure, and Intellectual disability. * **Management:** Immediate withdrawal of milk; switch to **Soy-based formula** or lactose-free formula. * **Note:** Even with treatment, many patients develop long-term complications like ovarian failure and speech deficits.

Q: Pellagra-like clinical syndrome is found in which of the following conditions?

Hartnup disease. **Explanation:** **Hartnup disease** is the correct answer because it is an autosomal recessive disorder characterized by a defect in the **SLC6A19 transporter**. This protein is responsible for the absorption of neutral amino acids (especially **Tryptophan**) in the small intestine and their reabsorption in the renal proximal tubules. Tryptophan is a vital precursor for the endogenous synthesis of **Niacin (Vitamin B3)**; approximately 60 mg of Tryptophan yields 1 mg of Niacin. In Hartnup disease, the profound deficiency of Tryptophan leads to secondary Niacin deficiency, resulting in the classic **Pellagra-like triad** of Dermatitis (photosensitive rash), Diarrhea, and Dementia (ataxia/psychosis). **Analysis of Incorrect Options:** * **Homocystinuria:** Caused by a deficiency of Cystathionine $\beta$-synthase. It presents with ectopia lentis, intellectual disability, and thromboembolism, but not pellagra-like symptoms. * **Histidinuria:** A benign condition involving elevated histidine in urine; it does not interfere with the Niacin pathway. * **Cystinosis:** A lysosomal storage disorder characterized by the accumulation of cystine crystals in organs (kidneys, eyes). It leads to Fanconi syndrome but not Niacin deficiency. **High-Yield Clinical Pearls for NEET-PG:** * **Diagnosis:** Confirmed by detecting **neutral aminoaciduria** (using paper chromatography) while excluding basic amino acids. * **Management:** High-protein diet and **Nicotinamide** supplementation. * **Differential for Pellagra:** Nutritional B3 deficiency, Carcinoid syndrome (Tryptophan diverted to Serotonin), and Isoniazid therapy (depletes B6, a cofactor for Niacin synthesis).

Q: In sickle cell trait, how many bands are typically found in hemoglobin electrophoresis?

2. **Explanation:** In **Sickle Cell Trait (HbAS)**, the individual is a heterozygote, meaning they possess one normal adult hemoglobin gene ($\beta^A$) and one mutated sickle gene ($\beta^S$). Consequently, their red blood cells contain two distinct types of hemoglobin: **HbA** ($\alpha_2\beta^A_2$) and **HbS** ($\alpha_2\beta^S_2$). On alkaline hemoglobin electrophoresis (pH 8.6), these two variants migrate at different speeds due to their net charge, resulting in **two distinct bands**. * **Why Option A is correct:** HbS results from a point mutation where glutamic acid (negative charge) is replaced by valine (neutral) at the 6th position of the beta-globin chain. This loss of negative charge makes HbS move slower toward the anode than HbA, creating two separate bands. Typically, HbA > HbS (approx. 60:40 ratio). * **Why Option B is incorrect:** A single band is seen in normal individuals (HbAA) or those with homozygous sickle cell disease (HbSS), where only one major type of hemoglobin is present. * **Why Options C & D are incorrect:** Four or five bands are not characteristic of simple sickle cell trait. Multiple bands might be seen in complex compound heterozygous states (e.g., HbSC disease with fetal hemoglobin) or when using specialized techniques like Isoelectric Focusing, but not in standard screening for sickle trait. **High-Yield Clinical Pearls for NEET-PG:** * **Electrophoresis Speed:** Remember the mnemonic **"A Fat Santa Claus"** for migration speed toward the Anode (Fastest to Slowest): **HbA > HbF > HbS > HbC**. * **Sickle Cell Trait:** These individuals are usually asymptomatic and provide a protective advantage against *Plasmodium falciparum* malaria. * **Diagnosis:** While electrophoresis shows two bands, the **Sickling Test** (using sodium metabisulfite) and **Solubility Test** will also be positive.

Q: Which of the following statements is FALSE regarding G6PD deficiency?

It is an autosomal recessive condition.. **Explanation:** **1. Why Option A is False (The Correct Answer):** Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is not autosomal recessive; it is an **X-linked recessive** disorder. This means it primarily affects males, while females are typically asymptomatic carriers (unless affected by skewed lyonization). This is a high-yield distinction in medical genetics. **2. Analysis of Other Options:** * **Option B:** G6PD is the rate-limiting enzyme in the Pentose Phosphate Pathway (PPP), responsible for producing **NADPH**. NADPH is essential for maintaining a pool of reduced glutathione, which neutralizes reactive oxygen species. Without it, exposure to oxidant stress (e.g., Fava beans, infections, or drugs like Primaquine and Sulfa drugs) leads to uncontrolled oxidative damage and **hemolysis**. * **Option C:** Oxidative stress causes hemoglobin to denature and precipitate into insoluble inclusions called **Heinz bodies**. When splenic macrophages attempt to remove these inclusions, they leave behind "Bite cells" (degmacytes). * **Option D:** In the most common variants (like G6PD A-), the enzyme has a shortened half-life. Since RBCs cannot synthesize new proteins, **older RBCs** have the lowest enzyme activity and are the first to undergo hemolysis during an oxidative challenge. **Clinical Pearls for NEET-PG:** * **Inheritance:** X-linked Recessive (like Hemophilia and DMD). * **Morphology:** Heinz bodies (Crystal violet stain) and Bite cells. * **Protective Effect:** G6PD deficiency provides a survival advantage against *Plasmodium falciparum* malaria. * **Diagnosis:** Enzyme assays should not be performed during an acute hemolytic episode, as the older cells (with low enzyme levels) have already lysed, potentially leading to a false-normal result.

Question 1

All of the following are autosomal dominant disorders except?

Accepted Answer

Cystic fibrosis

Answer

Tuberous sclerosis

Answer

Polyposis coli

Answer

Myotonic dystrophy

Question 2

G-6-P deficiency occurs in which of the following diseases?

Accepted Answer

Von-Gierke disease

Answer

Forbes disease

Answer

Niemann Picks disease

Answer

Tay Sachs disease

Question 3

A child presents with hepatomegaly and hypoglycemia. There is no improvement in blood sugar even after administration of epinephrine. What is the likely diagnosis?

Accepted Answer

Von Gierke's disease

Answer

Anderson's disease

Answer

Pompe's disease

Answer

McArdle's disease

Question 4

In Von Gierke's disease, the levels of ketone bodies are increased due to all EXCEPT:

Accepted Answer

Oxaloacetate is required for gluconeogenesis

Answer

The patients have hypoglycemia

Answer

The patients have low blood glucose

Answer

More mobilization of fats

Question 5

A 10-year-old child presents with recurrent skin lesions on the face and upper extremities that rapidly progress to cancer. Xeroderma pigmentosa is considered a possible differential. Which of the following enzymes is defective in this condition?

Accepted Answer

Endonuclease

Answer

Topoisomerase

Answer

3' 	→ 5' Exonuclease

Answer

Helicase

Question 6

NARP syndrome is a type of:

Accepted Answer

Mitochondrial function disorder

Answer

Glycogen storage disorder

Answer

Lysosomal storage disorder

Answer

Lipid storage disorder

Question 7

All of the following are true about Galactosemia EXCEPT?

Accepted Answer

Patients are symptomatic immediately after birth

Answer

Galactose 1 phosphate and galactitol have toxic effects on various organs

Answer

Jaundice and liver dysfunction commonly seen

Answer

E.coli sepsis is an important cause of mortality

Question 8

Pellagra-like clinical syndrome is found in which of the following conditions?

Accepted Answer

Hartnup disease

Answer

Homocystinuria

Answer

Histidinuria

Answer

Cystinosis

Question 9

In sickle cell trait, how many bands are typically found in hemoglobin electrophoresis?

Accepted Answer

2

Answer

1

Answer

4

Answer

5

Question 10

Which of the following statements is FALSE regarding G6PD deficiency?

Accepted Answer

It is an autosomal recessive condition.

Answer

It commonly manifests as hemolysis upon exposure to oxidant stress.

Answer

Heinz bodies are typically observed.

Answer

Older red blood cells are more susceptible to hemolysis.

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

On this page

Practice by Chapter

Want unlimited practice?