FMGE 2025 Practice Questions

Q: What is the status of the marked individual?

Adopted from another family. ***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.

Q: 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?

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. ***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.

Q: 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?

Ornithine transcarbamylase (OTC) deficiency. ***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

Q: 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?

Skeletal fluorosis. ***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.

Q: 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?

Thiamine. ***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.

Q: For testing blood clotting/coagulation parameters, blood is collected in which color-coded vacutainer tube?

Blue. ***Blue*** - The blue-coded vacutainer contains **Sodium Citrate** (3.2% or 3.8%), which is the required anticoagulant for performing coagulation studies, such as **PT** (Prothrombin Time) and **aPTT** (Activated Partial Thromboplastin Time) [1]. - **Sodium Citrate** works by binding and sequestering **calcium ions** (Factor IV), thereby reversibly preventing the coagulation cascade from proceeding until calcium is added back in the lab [1]. *Red* - The Red top tube typically contains **no anticoagulant** (or a clot activator) and is used to obtain **serum** after the blood clots naturally. - It is utilized for chemistry, serology, and blood bank tests, where the natural clotting process is required or coagulation factors are not needed. *Green* - The Green top tube contains **Heparin** (Lithium or Sodium Heparin), which inhibits clotting by augmenting the activity of **antithrombin III** [2]. - Although it provides plasma, it is unsuitable for routine coagulation assays because heparin itself significantly interferes with most coagulation factor tests. *Gray* - The Gray top tube contains **Potassium Oxalate** as an anticoagulant and **Sodium Fluoride** as a preservative. - It is specifically reserved for **glucose** and sometimes **lactate** measurements, as sodium fluoride inhibits enolase, thereby preventing glycolysis (glucose breakdown) by blood cells. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, pp. 128-130. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 583-584.

Q: Which of the following is pro-apoptotic?

Bax. ***Bax*** - Bax is a key **pro-apoptotic** effector protein from the Bcl-2 family [1]. Upon activation by stress signals, it translocates to the mitochondria and forms pores in the outer membrane [2]. - This pore formation, along with Bak, leads to **Mitochondrial Outer Membrane Permeabilization (MOMP)**, which releases **cytochrome c** and initiates the intrinsic caspase cascade of apoptosis [3]. *Bcl-2* - Bcl-2 is the prototypical **anti-apoptotic** protein that prevents apoptosis by binding to and inhibiting pro-apoptotic proteins like Bax and Bak [2]. - By preventing MOMP, it maintains mitochondrial integrity and is often overexpressed in cancers, such as follicular lymphoma, contributing to cell survival [2]. *Bcl-xL* - Bcl-xL is another major **anti-apoptotic** protein in the Bcl-2 family, with a function very similar to Bcl-2 [2]. - It promotes cell survival by sequestering pro-apoptotic BH3-only proteins and preventing the activation of Bax and Bak. *Mcl-1* - Mcl-1 (Myeloid cell leukemia-1) is a critical **anti-apoptotic** protein that is essential for the survival of various cell types [2]. - Its primary role is to inhibit apoptosis by neutralizing pro-apoptotic proteins, and its high levels are often associated with tumor progression and resistance to chemotherapy [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 65-67. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 310. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 64-65.

Q: A young boy presents with joint swelling after a fall. Lab investigations show normal PT and raised aPTT. What is the most likely diagnosis?

Hemophilia. ***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.

Q: A 5-year-old child is brought to the clinic with abdominal pain, irritability, and developmental delay. On examination, the child has pallor and a bluish line on the gums. Laboratory tests reveal microcytic anemia, and a peripheral blood smear shows red blood cells with basophilic stippling. Which of the following is the most likely diagnosis?

Lead poisoning. ***Lead poisoning***- All the symptoms—**abdominal pain** (colic), **irritability**, **developmental delay**, microcytic anemia, and the finding of a **bluish line on the gums** (Burton line)—are highly suggestive of chronic lead toxicity in a child. - The hallmark **basophilic stippling** on the blood smear is caused by lead inhibiting the enzyme **pyrimidine 5'-nucleotidase**, preventing RNA degradation.*Iron deficiency anemia*- While it causes **microcytic anemia** and pallor, it typically does not present with the severe neurodevelopmental regression or **abdominal colic** described.- Basophilic stippling is rare in iron deficiency anemia; the characteristic peripheral smear findings are severe **microcytosis** and **hypochromia**.*Sideroblastic anemia*- This condition is characterized by the presence of **ring sideroblasts** in the bone marrow and high iron levels, which requires specific testing for confirmation.- Although it can rarely present with basophilic stippling, it lacks the specific history of severe neurological and gastrointestinal symptoms (colic, developmental delay) associated with **lead exposure**.*Thalassemia minor*- This is a mild, often asymptomatic **microcytic, hypochromic anemia** caused by reduced globin chain synthesis, usually identified via routine screening or elevated **HbA2** on electrophoresis.- Thalassemia does not cause **basophilic stippling** (unless unstable Hb variants are present) and fundamentally lacks the systemic toxicity signs like **Burton lines** and **developmental delay**.

Question 1

What is the status of the marked individual?

Accepted Answer

Adopted from another family

Answer

Has a disease of chronic origin

Answer

Curable disease

Answer

Twin

Question 2

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?

Accepted Answer

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

Answer

Glycogen storage disease type I (Von Gierke disease)

Answer

Hers disease

Answer

Hereditary fructose intolerance

Question 3

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?

Accepted Answer

Ornithine transcarbamylase (OTC) deficiency

Answer

Orotidine 5′-phosphate decarboxylase deficiency

Answer

Carbamoyl phosphate synthetase I deficiency

Answer

Argininosuccinate lyase deficiency

Question 4

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?

Accepted Answer

Skeletal fluorosis

Answer

Calcium deficiency

Answer

Vitamin C deficiency

Answer

Vitamin D deficiency (Osteomalacia)

Question 5

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?

Accepted Answer

Thiamine

Answer

Iron

Answer

Vitamin D

Answer

Calcium

Question 6

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?

Accepted Answer

Liver biopsy for copper estimation

Answer

Serum ceruloplasmin

Answer

Copper excretion in urine

Answer

Serum copper

Question 7

For testing blood clotting/coagulation parameters, blood is collected in which color-coded vacutainer tube?

Accepted Answer

Blue

Answer

Gray

Answer

Red

Answer

Green

Question 8

Which of the following is pro-apoptotic?

Accepted Answer

Bax

Answer

Bcl-2

Answer

Bcl-xL

Answer

Mcl-1

Question 9

A young boy presents with joint swelling after a fall. Lab investigations show normal PT and raised aPTT. What is the most likely diagnosis?

Accepted Answer

Hemophilia

Answer

Von Willebrand Disease

Answer

Platelet function disorder

Answer

Iron Deficiency Anaemia (IDA)

Question 10

A 5-year-old child is brought to the clinic with abdominal pain, irritability, and developmental delay. On examination, the child has pallor and a bluish line on the gums. Laboratory tests reveal microcytic anemia, and a peripheral blood smear shows red blood cells with basophilic stippling. Which of the following is the most likely diagnosis?

Accepted Answer

Lead poisoning

Answer

Thalassemia minor

Answer

Iron deficiency anemia

Answer

Sideroblastic anemia

FMGE 2025

Anatomy

Biochemistry

Community Medicine

Internal Medicine

Pathology

Pediatrics