Biochemistry
2 questionsA 6-month-old infant is brought to the emergency department with lethargy, vomiting, and poor feeding. The episode occurred after prolonged fasting. Laboratory results reveal hypoglycemia, low ketone levels (hypoketosis), and mild hepatomegaly. These findings suggest a defect in fat metabolism. Which of the following is the most likely underlying disorder?
A 2-month-old infant presents with poor feeding, vomiting, and lethargy. Laboratory studies show hyperammonemia and elevated levels of orotic acid in the urine. Which of the following is the most likely enzyme deficiency?
FMGE 2025 - Biochemistry FMGE Practice Questions and MCQs
Question 491: A 6-month-old infant is brought to the emergency department with lethargy, vomiting, and poor feeding. The episode occurred after prolonged fasting. Laboratory results reveal hypoglycemia, low ketone levels (hypoketosis), and mild hepatomegaly. These findings suggest a defect in fat metabolism. Which of the following is the most likely underlying disorder?
- A. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (Correct Answer)
- B. Glycogen storage disease type I (Von Gierke disease)
- C. Hers disease
- D. Hereditary fructose intolerance
Explanation: ***Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency*** - This disorder is the most common defect of **fatty acid oxidation** and is characterized by the inability to break down medium-chain fatty acids during fasting, leading to severe **hypoglycemia**. - The hallmark finding is **hypoketosis** (low ketones), as the inability to generate acetyl-CoA from fatty acid breakdown means the substrate required for **ketogenesis** is unavailable. *Hers disease* - This is **Glycogen Storage Disease type VI**, involving a deficiency in **liver glycogen phosphorylase**, leading to impaired glycogenolysis and fasting hypoglycemia. - However, GSD type VI does not impair **beta-oxidation**; hence, patients usually maintain the ability to produce adequate **ketone bodies** during periods of fasting. *Hereditary fructose intolerance* - This disorder is a defect of **aldolase B** and causes symptoms (vomiting, lethargy, hypoglycemia) only after the introduction of **dietary fructose** or sucrose. - The acute symptoms are due to **phosphate trapping** and subsequent inhibition of gluconeogenesis, which is dependent on dietary exposure rather than prolonged fasting alone. *Glycogen storage disease type I (Von Gierke disease)* - This condition, caused by a deficiency of **glucose-6-phosphatase**, leads to profound fasting hypoglycemia, significant hepatomegaly, and **lactic acidosis**. - Unlike MCAD deficiency, Von Gierke disease primarily causes defects in glucose release but generally maintains or even increases **ketone body production** (hyperketosis) because fat breakdown is often accelerated.
Question 492: A 2-month-old infant presents with poor feeding, vomiting, and lethargy. Laboratory studies show hyperammonemia and elevated levels of orotic acid in the urine. Which of the following is the most likely enzyme deficiency?
- A. Orotidine 5′-phosphate decarboxylase deficiency
- B. Carbamoyl phosphate synthetase I deficiency
- C. Argininosuccinate lyase deficiency
- D. Ornithine transcarbamylase (OTC) deficiency (Correct Answer)
Explanation: ***Ornithine transcarbamylase (OTC) deficiency*** - **Most common X-linked urea cycle disorder** presenting in infancy with hyperammonemia - **Classic triad:** Hyperammonemia + elevated urinary orotic acid + low blood urea nitrogen - **Biochemical mechanism:** OTC converts carbamoyl phosphate + ornithine → citrulline. When deficient, carbamoyl phosphate accumulates and spills into the pyrimidine synthesis pathway, producing excess orotic acid - Clinical features: poor feeding, vomiting, lethargy, seizures, developmental delay *Carbamoyl phosphate synthetase I (CPS I) deficiency* - Also causes hyperammonemia but **NO orotic aciduria** (defect occurs before OTC step) - Carbamoyl phosphate is not formed, so cannot enter pyrimidine pathway - Cannot be distinguished clinically from OTC deficiency without measuring orotic acid *Argininosuccinate lyase deficiency* - Causes hyperammonemia with elevated **argininosuccinate** in blood/urine - Does not cause orotic aciduria (defect is downstream of OTC) - May present with trichorrhexis nodosa (brittle hair) *Orotidine 5′-phosphate decarboxylase deficiency* - Causes hereditary **orotic aciduria** but **NO hyperammonemia** (not a urea cycle disorder) - Defect in de novo pyrimidine synthesis pathway - Presents with megaloblastic anemia, growth retardation, responds to uridine supplementation
Community Medicine
3 questionsWhat is the status of the marked individual?
A person from an Assam village is depicted with genu valgum (knock-knees), a condition observed in multiple individuals in the community. What is the most likely diagnosis?
A family consumes a diet predominantly of rice and pulses and developed signs of muscle weakness and movement. Which of the following should be given for prophylaxis?
FMGE 2025 - Community Medicine FMGE Practice Questions and MCQs
Question 491: What is the status of the marked individual?
- A. Has a disease of chronic origin
- B. Adopted from another family (Correct Answer)
- C. Curable disease
- D. Twin
Explanation: ***Adopted from another family*** - In pedigree analysis, square **brackets `[ ]`** placed around an individual's symbol (a circle for female, a square for male) specifically denote that the person has been **adopted** into the family. - The relationship lines connecting an adopted individual to their adoptive parents are typically represented as **dashed lines** to distinguish them from biological parent-offspring lines, which are solid. *Has a disease of chronic origin* - An individual affected by a genetic disease or trait is represented by a **shaded or filled-in** symbol, not by brackets. The circle in the image is not shaded, indicating an unaffected status. - Pedigree symbols do not typically differentiate between chronic and acute diseases; they primarily indicate the **presence or absence** of the specific trait being studied. *Curable disease* - The **prognosis or curability** of a disease is not represented by a standard pedigree symbol. An affected status is shown by **shading the symbol**, irrespective of the disease's nature. - The symbol for adoption (`[ ]`) is distinct and unrelated to any health status or medical condition. *Twin* - **Twins** are indicated by two individual symbols branching from the same point on the parental line. A horizontal line connecting the symbols signifies **monozygotic (identical) twins**. - The symbol shown represents a single individual, and the brackets denote adoption, not a twin relationship.
Question 492: A person from an Assam village is depicted with genu valgum (knock-knees), a condition observed in multiple individuals in the community. What is the most likely diagnosis?
- A. Calcium deficiency
- B. Vitamin C deficiency
- C. Vitamin D deficiency (Osteomalacia)
- D. Skeletal fluorosis (Correct Answer)
Explanation: ***Skeletal fluorosis*** - This condition is caused by chronic, excessive intake of **fluoride**, often through contaminated drinking water, which can lead to endemic outbreaks in specific geographical areas like villages in Assam. - It manifests with skeletal changes including osteosclerosis, calcification of ligaments, and deformities such as **genu valgum** (knock-knees) or genu varum (bow-legs). *Calcium deficiency* - Primarily leads to **osteoporosis** in adults, which is a reduction in bone mass, increasing the risk of fractures rather than causing specific deformities like genu valgum. - While severe deficiency can contribute to bone softening, it is typically associated with Vitamin D deficiency and is less likely to cause a community-wide endemic presentation compared to a waterborne toxin. *Vitamin C deficiency* - This deficiency results in **scurvy**, which affects **collagen synthesis** and presents with symptoms like bleeding gums, poor wound healing, and perifollicular hemorrhages. - It does not cause the kind of gross skeletal deformities seen in the image, such as **genu valgum**. *Vitamin D deficiency (Osteomalacia)* - This condition leads to defective bone mineralization (**osteomalacia**), causing bone pain, muscle weakness, and potential deformities. - Although it can cause genu valgum, the context of an entire community in a specific village being affected makes an environmental exposure like **endemic fluorosis** a more probable diagnosis.
Question 493: A family consumes a diet predominantly of rice and pulses and developed signs of muscle weakness and movement. Which of the following should be given for prophylaxis?
- A. Iron
- B. Vitamin D
- C. Calcium
- D. Thiamine (Correct Answer)
Explanation: ***Thiamine*** - A diet relying mainly on **polished rice** lacks essential micronutrients, particularly **thiamine (Vitamin B1)**, which is removed during the polishing process. - Deficiency of thiamine causes **Beriberi**, manifesting as neurological deficits (dry Beriberi leading to muscle weakness and neuropathy) or cardiovascular symptoms (wet Beriberi leading to high-output cardiac failure). *Calcium* - Calcium deficiency typically results in **hypocalcemia**, presenting as symptoms like **tetany**, muscle spasms, and paresthesia, which are distinct from Beriberi's clinical picture. - Although important for musculoskeletal health, supplementing calcium alone would not prevent the severe neurological and motor impairment seen in **thiamine deficiency**. *Vitamin D* - Deficiency of Vitamin D causes disorders of bone mineralization—**Rickets** in children and **Osteomalacia** in adults, primarily characterized by bone pain and fractures. - While Vitamin D deficiency can cause myopathy, it does not explain the specific cluster of symptoms (weakness and movement issues) related to a rice-dominant diet lacking the coenzyme necessary for carbohydrate metabolism. *Iron* - Iron deficiency leads to **microcytic hypochromic anemia**, whose primary symptoms include fatigue, dizziness, and pallor, not the characteristic movement and muscle weakness indicative of **Beriberi**. - Iron supplementation would address anemia but would fail to protect against severe neurological illness resulting from the lack of **thiamine**, which is crucial for energy generation in neural tissues.
Internal Medicine
2 questionsA young boy presents with joint swelling after a fall. Lab investigations show normal PT and raised aPTT. What is the most likely diagnosis?
A 15-year-old boy presents with tremors, difficulty in speech, and behavioral changes. On examination, he has hepatomegaly and a golden-brown ring at the limbus of the cornea (Kayser-Fleischer ring). Wilson's disease is suspected. Which of the following is the best investigation to support the diagnosis?
FMGE 2025 - Internal Medicine FMGE Practice Questions and MCQs
Question 491: A young boy presents with joint swelling after a fall. Lab investigations show normal PT and raised aPTT. What is the most likely diagnosis?
- A. Von Willebrand Disease
- B. Hemophilia (Correct Answer)
- C. Platelet function disorder
- D. Iron Deficiency Anaemia (IDA)
Explanation: ***Hemophilia***- The presentation of joint swelling after trauma (suggesting **hemarthrosis**) in a young boy is highly characteristic of hemophilia, which is an X-linked recessive disorder [1].- Hemophilia A (Factor VIII deficiency) or B (Factor IX deficiency) affects the **intrinsic coagulation pathway**, leading to an isolated prolongation of the **aPTT** while the PT remains normal. *Von Willebrand Disease*- VWD primarily causes defects in **platelet adhesion** and mild to moderate mucocutaneous bleeding (e.g., epistaxis, menorrhagia), not typically severe spontaneous hemarthrosis [1].- While severe VWD can lower Factor VIII and mildly prolong aPTT, it generally presents differently and often affects both males and females (autosomal pattern) [2].*Iron Deficiency Anaemia (IDA)*- IDA is a nutritional deficiency resulting in **microcytic, hypochromic anemia** and is not a primary bleeding disorder.- It does not involve defects in the coagulation cascade; therefore, PT and aPTT levels would be within the **normal reference range**.*Platelet function disorder*- These disorders (e.g., Glanzmann's or Bernard-Soulier) affect **primary hemostasis** (platelet plug formation), leading mainly to mucocutaneous bleeding [2].- In platelet disorders, the **PT and aPTT** are typically normal, as the coagulation cascade (secondary hemostasis) is intact.
Question 492: A 15-year-old boy presents with tremors, difficulty in speech, and behavioral changes. On examination, he has hepatomegaly and a golden-brown ring at the limbus of the cornea (Kayser-Fleischer ring). Wilson's disease is suspected. Which of the following is the best investigation to support the diagnosis?
- A. Serum ceruloplasmin
- B. Liver biopsy for copper estimation (Correct Answer)
- C. Copper excretion in urine
- D. Serum copper
Explanation: ***Liver biopsy for copper estimation*** - This is considered the **gold standard** diagnostic test for Wilson's disease, as it directly measures the pathologically increased copper accumulation in the liver - A hepatic copper concentration greater than **250 µg per gram** dry weight is generally diagnostic of Wilson's disease - **Important clinical context:** In this case, the presence of **Kayser-Fleischer rings with neurological symptoms** makes the diagnosis of Wilson's disease virtually certain [1]. In such scenarios, liver biopsy may **not be necessary** as the diagnosis can be confirmed with non-invasive investigations (ceruloplasmin + urinary copper) - Liver biopsy is primarily indicated when the diagnosis is **uncertain** or when non-invasive tests are inconclusive [2] - However, as the question asks for the "best investigation to support the diagnosis," liver biopsy remains the most **definitive** test, though not always the most **practical** first choice *Serum ceruloplasmin* - This is typically the **first-line investigation** for suspected Wilson's disease and is usually low (<20 mg/dL or <200 mg/L) - However, up to 10–20% of symptomatic patients may present with **normal serum ceruloplasmin** levels, particularly in children - Low ceruloplasmin levels are also seen in other conditions, such as **protein-losing states**, severe malnutrition, or other copper metabolism disorders, limiting its specificity - In the presence of KF rings, a low ceruloplasmin is highly supportive and often sufficient for diagnosis *Serum copper* - Total serum copper is often low because ceruloplasmin (the main copper-carrying protein) level is low, but this finding is **non-specific** - In the setting of **fulminant hepatic failure**, massive release of stored copper can occur, leading to paradoxically normal or even elevated serum copper levels [1] - Free (non-ceruloplasmin-bound) copper is elevated in Wilson's disease but is difficult to measure directly *Copper excretion in urine* - Elevated 24-hour urinary copper excretion (usually **>100 µg/day**) is a highly supportive finding, reflecting increased levels of non-ceruloplasmin-bound copper - Values **>1,000 µg/day** strongly suggest acute liver failure due to Wilson's disease - The reliability of this test can be hampered by **incomplete or inaccurate 24-hour urine collection**, making it less conclusive than direct liver copper measurement - This is an excellent non-invasive supportive test when KF rings are present
Pathology
3 questionsWhich CD markers are typically positive in Chronic Lymphocytic Leukaemia (CLL)?
2-year-old with fever, lymphadenopathy and H&E shows hallmark cells. The diagnosis of anaplastic large cell lymphoma was made. Most likely translocation?
In Barrett's oesophagus, which of the following epithelial transformations occurs?
FMGE 2025 - Pathology FMGE Practice Questions and MCQs
Question 491: Which CD markers are typically positive in Chronic Lymphocytic Leukaemia (CLL)?
- A. CD10, CD19, CD22
- B. CD19, CD20, CD23, CD5 (Correct Answer)
- C. CD13, CD33, CD117
- D. CD3, CD5, CD8
Explanation: CD19, CD20, CD23, CD5 [1] - Chronic Lymphocytic Leukemia (CLL) is a malignancy of mature B-lymphocytes, which typically express the pan-B-cell markers CD19 and CD20 (often dimly), along with CD23 [1]. - A hallmark of CLL is the aberrant co-expression of the T-cell marker CD5 [2], which is crucial for differentiating it from other B-cell lymphomas. The peripheral smear in the image shows mature lymphocytes and a characteristic smudge cell, supporting the diagnosis of CLL [1]. CD3, CD5, CD8 - This profile is characteristic of a T-cell malignancy, as CD3 is a pan-T-cell marker and CD8 is a marker for cytotoxic T-cells [2]. - While CD5 is present in CLL, its combination with CD3 and CD8 excludes a B-cell disorder like CLL. CD10, CD19, CD22 - This combination of markers is more suggestive of other B-cell neoplasms like Follicular Lymphoma or Burkitt Lymphoma, which are characteristically CD10 positive [2]. - Typical CLL is negative for CD10 and positive for CD5 and CD23, which are key distinguishing features [1]. CD13, CD33, CD117 - These are markers associated with the myeloid lineage. CD13 and CD33 are classic myeloid antigens often seen in Acute Myeloid Leukemia (AML). - CD117 (c-kit) is a marker for hematopoietic progenitors and is also frequently positive in AML, making this immunophenotype inconsistent with a lymphoid neoplasm. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 602. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 598.
Question 492: 2-year-old with fever, lymphadenopathy and H&E shows hallmark cells. The diagnosis of anaplastic large cell lymphoma was made. Most likely translocation?
- A. t(14;18)
- B. t(8;22)
- C. t(2;5) (Correct Answer)
- D. t(8;14)
Explanation: ***Correct: t(2;5)*** - This is the **most common and classic translocation** found in systemic **Anaplastic Large Cell Lymphoma (ALCL)**, especially in children [1] - Occurs in approximately **60-85% of systemic ALCL cases** - Fuses the **NPM (Nucleophosmin)** gene on chromosome 5 with the **ALK** gene on chromosome 2 [1] - Results in constitutively active **ALK tyrosine kinase** that drives cell proliferation [1] - **ALK-positive ALCL** has a better prognosis, particularly in pediatric patients [1] *Incorrect: t(8;14)* - This is the hallmark translocation of **Burkitt Lymphoma (BL)**, not ALCL [2] - Juxtaposes the **MYC oncogene** on chromosome 8 to the **IgH promoter** on chromosome 14 [2] - Burkitt Lymphoma presents with rapidly growing masses and characteristic **"starry sky"** microscopic appearance [3] - Distinct from ALCL's hallmark cells (large cells with eccentric horseshoe/kidney-shaped nuclei) *Incorrect: t(8;22)* - A variant translocation associated with **Burkitt Lymphoma (BL)** [2] - Translocates **MYC gene** to the **kappa light chain locus** on chromosome 22 [2] - Results in MYC overexpression, which is pathognomonic for Burkitt Lymphoma - Not associated with Anaplastic Large Cell Lymphoma *Incorrect: t(14;18)* - Characteristic translocation of **Follicular Lymphoma (FL)** - Leads to overexpression of the **BCL2 anti-apoptotic protein** - Follicular Lymphoma is typically seen in adults and is a **B-cell lymphoma** - ALCL is a **T-cell/null-cell lymphoma**, making this translocation irrelevant **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 565-566. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 606.
Question 493: In Barrett's oesophagus, which of the following epithelial transformations occurs?
- A. Squamous to intestinal columnar epithelium (Correct Answer)
- B. Cuboidal to columnar epithelium
- C. Transitional to squamous epithelium
- D. Columnar to squamous epithelium
Explanation: ***Squamous to intestinal columnar epithelium*** - Barrett's esophagus is a complication of chronic **gastroesophageal reflux disease (GERD)**, where the normal stratified **squamous epithelium** of the lower esophagus is replaced by metaplastic columnar epithelium [1]. - This metaplastic epithelium is specifically an **intestinal type**, characterized by the presence of **goblet cells**, which is considered a premalignant condition for esophageal adenocarcinoma [1]. *Columnar to squamous epithelium* - This describes the reverse process of what happens in Barrett's esophagus. - This type of metaplasia can occur in other organs, for example, in the endocervix (squamous metaplasia) or the bronchi of chronic smokers. *Transitional to squamous epithelium* - **Transitional epithelium** (urothelium) is the characteristic lining of the urinary tract (e.g., bladder, ureters) and is not found in the esophagus. - This type of metaplastic change is seen in the bladder in response to chronic irritation, such as from stones or **Schistosoma haematobium** infection. *Cuboidal to columnar epithelium* - The normal esophageal lining is stratified squamous epithelium, not cuboidal epithelium. - While metaplasia involving cuboidal cells can occur in glandular ducts or bronchioles, it is not the transformation that defines Barrett's esophagus. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Alimentary System Disease, pp. 347-349.