FMGE 2024 - Biochemistry PYQs Practice Questions

Q: Zellweger syndrome is associated with which cellular organelle?

A. Peroxisomes. ***A. Peroxisomes*** - Zellweger syndrome is a severe disorder belonging to the group of **peroxisomal biogenesis disorders (PBDs)**, resulting from a failure to form functional peroxisomes due to mutations in *PEX* genes. - Functional peroxisomes are essential for the metabolism of substances like **very long-chain fatty acids (VLCFAs)** and plasmalogens; their absence leads to the accumulation of these toxic molecules. *B. Mitochondria* - **Mitochondria** are the powerhouse organelles responsible for cellular energy production via oxidative phosphorylation. - Mitochondrial disorders present with distinct features like lactic acidosis, myopathy, and neurodegeneration, which differ from the characteristic peroxisomal dysfunction seen in Zellweger syndrome. *C. Lysosomes* - **Lysosomes** are crucial for degrading cellular waste products and macromolecules; defects in these organelles cause **lysosomal storage diseases** (e.g., mucopolysaccharidoses). - Although some symptoms overlap, Zellweger syndrome is specifically defined by **peroxisomal dysfunction**, not primary lysosomal enzyme deficiency. *D. Ribosomes* - **Ribosomes** are responsible for synthesizing proteins via translation of mRNA. - Defects in ribosomes typically impair **global protein synthesis** or specific tissue development (ribosomopathies), which is distinct from the primary metabolic defects seen in Zellweger syndrome. [Practice more Biochemistry PYQs on OnCourse]

Q: A 3-month-old baby presents with severe hepatomegaly, cataracts in both eyes, lethargy, and hypotonia. Based on these symptoms, which enzyme deficiency is most likely involved?

Galactose-1-Phosphate Uridyl Transferase. ***Galactose-1-Phosphate Uridyl Transferase*** - **GALT** deficiency causes **Classic Galactosemia**, which is characterized by the accumulation of **galactose-1-phosphate**, leading to widespread organ damage. - The classic presentation in neonates includes **hepatomegaly**, **jaundice**, failure to thrive, hypoglycemia, **E. coli sepsis**, developmental delay, and pathognomonic **cataracts**. - This is the **most severe form** of galactosemia and matches all the clinical features in this case. *Galactokinase* - Deficiency of **Galactokinase (GALK)** leads to a milder form of galactosemia where **galactitol** accumulates, primarily causing **cataracts** in infancy. - Systemic symptoms like **hepatomegaly**, liver failure, and severe lethargy, as seen in this 3-month-old, are typically **absent** in GALK deficiency. *UDP-Galactose-4-Epimerase* - **GALE** deficiency is the rarest form of galactosemia with variable clinical severity. - While severe forms can present with symptoms similar to classic galactosemia, they are extremely rare and account for less than 5% of galactosemia cases. - The combination of severe hepatomegaly and cataracts at 3 months is most characteristic of **GALT deficiency**, not GALE deficiency. *Hepatic Glucose-6-Phosphatase* - Deficiency of this enzyme causes **Von Gierke disease** (GSD Type I), characterized by significant **hepatomegaly** and severe **fasting hypoglycemia**. - While it causes hepatomegaly and lethargy (from hypoglycemia), it is **not** associated with the development of **cataracts**, which differentiates it from galactosemia. [Practice more Biochemistry PYQs on OnCourse]

Q: Which substance is involved in the conjugation process in the liver?

Glucuronic Acid. ***Glucuronic Acid***- The conjugation process is a Phase II detoxification reaction in the liver that increases the compound's polarity and water solubility for excretion.- **Glucuronidation**, catalyzed by **UDP-glucuronosyltransferases (UGT)**, is the most common and critical conjugation pathway, where substrates (like **bilirubin** and drugs) are linked to **glucuronic acid** (provided by UDP-glucuronic acid).*Hyaluronic Acid*- This acid is a large, non-sulfated **glycosaminoglycan** and a primary component of the **extracellular matrix** and **synovial fluid**.- It functions mainly in tissue structure, hydration, and lubrication, not as a conjugating molecule in liver metabolism.*Gluconic Acid*- This is an oxidation product of **glucose**, often used in food and pharmaceutical industries (e.g., as a salt like ferrous gluconate).- While structurally related to glucose metabolites, it is **glucuronic acid**, not gluconic acid, that is utilized for Phase II **conjugation**.*Glycolic Acid*- This substance is the smallest **alpha-hydroxy acid (AHA)** and is widely known for its use as a chemical exfoliator in dermatology.- Although it is an endogenous metabolite, it is not involved in the major Phase II conjugation reactions in the liver; these reactions primarily utilize **glucuronic acid**, sulfate, or glutathione. [Practice more Biochemistry PYQs on OnCourse]

Q: A 7-year-old child of short stature presents with skin patches and learning difficulties. Diagnostic workup indicates a defect in DNA repair specifically related to double-strand breaks. What is the most likely diagnosis?

Bloom Syndrome. ***Bloom Syndrome***- This condition is caused by a mutation in the **BLM gene**, which encodes a **RecQ helicase** necessary for homologous recombination repair (a mechanism for **double-strand break** repair), consistent with the clinical presentation.- Key clinical features include **short stature**, **telangiectatic erythema** (skin patches, especially on sun exposure), and intellectual disability/learning difficulties. *Xeroderma Pigmentosum*- This disease results from a defect in **Nucleotide Excision Repair (NER)**, crucial for repairing DNA damage caused by UV light (e.g., pyrimidine dimers), not primarily double-strand breaks.- Patients exhibit extreme **photosensitivity** and have a drastically increased risk of developing multiple skin cancers early in life.*Cockayne Syndrome*- Cockayne syndrome results from defects in genes like *ERCC8* or *ERCC6*, impairing **Transcription-Coupled Repair (TCR)**, a specific type of NER.- While it presents with short stature (often described as **cachectic dwarfism**) and neurological defects, the primary DNA defect is not in the repair of double-strand breaks but rather UV adducts in transcribed DNA.*Lynch Syndrome*- Also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), this syndrome is caused by defects in **Mismatch Repair (MMR)** genes (e.g., *MLH1*, *MSH2*).- It primarily predisposes individuals to colorectal and endometrial cancers and is not typically associated with the features of short stature and specific DNA double-strand break repair defects seen in this child. [Practice more Biochemistry PYQs on OnCourse]

Q: Which of the following deficiencies causes follicular hyperkeratosis?

Vitamin A. ***Vitamin A***- Deficiency in Vitamin A (retinol) impairs the differentiation of **keratinizing epithelia**, leading to **squamous metaplasia**.- This results in **follicular hyperkeratosis** (also known as **phrynoderma** or 'toad skin'), where keratin plugs block the hair follicles, giving the skin a rough, bumpy appearance.*Vitamin C*- Deficiency causes **scurvy**, primarily due to defective collagen synthesis, leading to fragile blood vessels.- The characteristic skin finding is **perifollicular hemorrhage** (petechiae around hair follicles) and **painless gum bleeding**, not hyperkeratosis due to keratin plugging.*Vitamin E*- This deficiency primarily acts as an **antioxidant deficiency**, leading to increased susceptibility of cell membranes to oxidative damage.- Clinical manifestations often include **hemolytic anemia** (due to erythrocyte membrane damage) and **neurological symptoms** (e.g., ataxia, peripheral neuropathy).*Vitamin B6*- Deficiency of pyridoxine is often associated with cutaneous symptoms like a **seborrheic dermatitis-like rash** and **cheilosis** (cracked lips).- It is crucial for coenzyme functions but does not directly cause the severe keratin plugging characterized by widespread follicular hyperkeratosis. [Practice more Biochemistry PYQs on OnCourse]

Question 1

Zellweger syndrome is associated with which cellular organelle?

Accepted Answer

A. Peroxisomes

Answer

C. Lysosomes

Answer

D. Ribosomes

Answer

B. Mitochondria

Question 2

A 3-month-old baby presents with severe hepatomegaly, cataracts in both eyes, lethargy, and hypotonia. Based on these symptoms, which enzyme deficiency is most likely involved?

Accepted Answer

Galactose-1-Phosphate Uridyl Transferase

Answer

Hepatic Glucose-6-Phosphatase

Answer

UDP-Galactose-4-Epimerase

Answer

Galactokinase

Question 3

Which substance is involved in the conjugation process in the liver?

Accepted Answer

Glucuronic Acid

Answer

Gluconic Acid

Answer

Hyaluronic Acid

Answer

Glycolic Acid

Question 4

A 7-year-old child of short stature presents with skin patches and learning difficulties. Diagnostic workup indicates a defect in DNA repair specifically related to double-strand breaks. What is the most likely diagnosis?

Accepted Answer

Bloom Syndrome

Answer

Lynch Syndrome

Answer

Xeroderma Pigmentosum

Answer

Cockayne Syndrome

Question 5

Which of the following deficiencies causes follicular hyperkeratosis?

Accepted Answer

Vitamin A

Answer

Vitamin C

Answer

Vitamin E

Answer

Vitamin B6

Question 6

A 6-month-old boy presents with recurrent bacterial and fungal infections, chronic diarrhea, and failure to thrive. He is diagnosed with severe combined immunodeficiency due to an autosomal recessive inheritance pattern. Which enzyme deficiency is responsible?

Accepted Answer

D. Adenosine deaminase

Answer

B. Ornithine transcarbamylase

Answer

C. Hypoxanthine-guanine phosphoribosyltransferase

Answer

A. Phosphomannose isomerase

Question 7

Iron absorption is decreased in which of the following?

Accepted Answer

Tea

Answer

Amla

Answer

Lemon

Answer

Sprouting

Question 8

Conjunctival xerosis is caused by which vitamin deficiency?

Accepted Answer

Vitamin A

Answer

Vitamin K

Answer

Vitamin C

Answer

Vitamin D

Question 9

Which type of ion channel is affected by mutations in the CFTR gene?

Accepted Answer

Chloride

Answer

Calcium

Answer

Potassium

Answer

Sodium

FMGE 2024 — Biochemistry