Internal Medicine
1 questionsA mutation in the SOD1 gene is most commonly associated with which of the following conditions?
FMGE 2025 - Internal Medicine FMGE Practice Questions and MCQs
Question 561: A mutation in the SOD1 gene is most commonly associated with which of the following conditions?
- A. Parkinson's disease
- B. Multiple sclerosis
- C. Huntington's disease
- D. Amyotrophic lateral sclerosis (ALS) (Correct Answer)
Explanation: ***Amyotrophic lateral sclerosis (ALS)*** - **SOD1 (Superoxide dismutase 1)** gene mutations are responsible for approximately **20% of familial ALS** cases and 1-2% of sporadic cases - SOD1 enzyme normally protects cells from oxidative damage by converting superoxide radicals to hydrogen peroxide - Mutations lead to **toxic gain of function** causing motor neuron degeneration, affecting both upper and lower motor neurons [1] - Clinical features include progressive muscle weakness, fasciculations, spasticity, and bulbar symptoms [1] - This is one of the **most well-established genetic associations** in neurodegenerative disease *Parkinson's disease* - Associated with mutations in **SNCA (α-synuclein), LRRK2, and Parkin** genes, not SOD1 - Characterized by dopaminergic neuron loss in substantia nigra - Presents with bradykinesia, rigidity, resting tremor, and postural instability *Multiple sclerosis* - An **autoimmune demyelinating disease** with complex genetic susceptibility involving HLA-DRB1 and other immune-related genes - Not linked to SOD1 mutations - Presents with relapsing-remitting neurological symptoms and white matter lesions *Huntington's disease* - Caused by **CAG trinucleotide repeat expansion** in the huntingtin (HTT) gene on chromosome 4 - Autosomal dominant inheritance with anticipation - Presents with chorea, cognitive decline, and psychiatric symptoms
Pathology
5 questionsBasophilic stippling of red blood cells is most characteristically seen in which of the following conditions?
In Pap smear cytology, which of the following is the most appropriate fixative used to preserve cellular details immediately after smearing?
Which genetic syndrome is caused by a deletion of the short arm of chromosome 5 (5p deletion)?
FBN1 gene mutation is seen in which of the following genetic disorders?
Acute hemolytic blood transfusion reactions are mediated by which type of hypersensitivity reaction?
FMGE 2025 - Pathology FMGE Practice Questions and MCQs
Question 561: Basophilic stippling of red blood cells is most characteristically seen in which of the following conditions?
- A. Lead poisoning (Correct Answer)
- B. Megaloblastic anemia
- C. Hereditary spherocytosis
- D. Iron deficiency anaemia
Explanation: ***Lead poisoning*** - Lead inhibits several enzymes in the heme synthesis pathway and also inhibits **ribonuclease**, which is responsible for degrading residual ribosomal RNA (rRNA) in reticulocytes [1]. This leads to aggregation of ribosomes, appearing as coarse blue granules known as **basophilic stippling**. - While also seen in conditions like thalassemias and sideroblastic anemia, coarse basophilic stippling is a classic and highly characteristic finding in lead poisoning. *Iron deficiency anaemia* - The characteristic peripheral smear findings are **microcytic** and **hypochromic** red blood cells, which appear smaller and paler than normal [2]. - **Pencil cells** (elliptocytes) and **thrombocytosis** (an increased platelet count) are also commonly observed, but basophilic stippling is not a typical feature [2]. *Megaloblastic anemia* - This anemia, due to **vitamin B12** or **folate** deficiency, is characterized by **macro-ovalocytes** (large, oval red blood cells) and **hypersegmented neutrophils** on the peripheral smear [3]. - Other inclusions like **Howell-Jolly bodies** may be present, but basophilic stippling is not the defining feature. *Hereditary spherocytosis* - This is a genetic disorder affecting red blood cell membrane proteins, leading to the formation of **spherocytes** – small, round RBCs lacking central pallor. - The key findings are spherocytes on the smear and an increased **mean corpuscular hemoglobin concentration (MCHC)**, not basophilic stippling. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 418-419. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 590-591. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 594-595.
Question 562: In Pap smear cytology, which of the following is the most appropriate fixative used to preserve cellular details immediately after smearing?
- A. 95% ethanol (Correct Answer)
- B. 70% ethanol
- C. 10% buffered formalin
- D. 50% formaldehyde
Explanation: ***95% ethanol*** - This is considered the **gold standard fixative** for conventional **Pap smear** cytology because it acts rapidly to precipitate proteins, effectively preserving cellular and **nuclear detail** crucial for diagnosis. - Immediate fixation in 95% ethanol (or proprietary sprays containing alcohol) is essential to prevent **air-drying artifact**, which can severely distort nuclear morphology and render the smear diagnostically inadequate [1]. *50% formaldehyde* - Formaldehyde is typically used for **tissue fixation** (histopathology) rather than cytology smears, and this concentration is too dilute for effective cellular preservation. - Formaldehyde is an **additive fixative**, which acts differently than the preferred precipitant fixatives (like ethanol) used on thin smears. *70% ethanol* - While an alcohol fixative, **95% ethanol** is the recommended concentration for optimum dehydration and quick stabilization of the cell structures in a Pap smear. - 70% concentration may not fix the cells rapidly enough, potentially leading to suboptimal **chromatin preservation** compared to the higher concentration. *10% buffered formalin* - This is the routine fixative used globally for large **surgical pathology** specimens (biopsies and resections). - Formalin is generally not the preferred immediate fixative for thin-layer cytology slides compared to quick-acting alcohol, which provides superior **nuclear clarity** for Papanicolaou staining. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1010-1011.
Question 563: Which genetic syndrome is caused by a deletion of the short arm of chromosome 5 (5p deletion)?
- A. Edward syndrome
- B. Turner syndrome
- C. Patau syndrome
- D. Cri-du-chat syndrome (Correct Answer)
Explanation: ***Cri-du-chat syndrome*** - This syndrome is classically defined by a partial terminal deletion of the short arm of chromosome 5, designated as **5p deletion**. - Key clinical features include severe **intellectual disability**, **microcephaly**, and the characteristic high-pitched, monotonic **cat-like cry** that gives the syndrome its name. *Edward syndrome* - Edward syndrome is caused by an extra copy of chromosome 18 (**Trisomy 18**) [1]. - Clinical findings are often severe, including **micrognathia**, overlapping fingers, and **rocker-bottom feet** [1]. *Patau syndrome* - Patau syndrome is caused by an extra copy of chromosome 13 (**Trisomy 13**) [1]. - It is associated with severe midline defects such as **holoprosencephaly**, **cleft lip and palate**, and **polydactyly** [1]. *Turner syndrome* - Turner syndrome is a sex chromosome abnormality resulting from the absence of one X chromosome (45,X), making it a form of **monosomy X** [2]. - It primarily affects females, causing features like **short stature**, primary **amenorrhea** due to streak ovaries, and a **webbed neck** [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 168-169. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 175-177.
Question 564: FBN1 gene mutation is seen in which of the following genetic disorders?
- A. Homocystinuria
- B. von Hippel-Lindau syndrome
- C. Ehlers-Danlos syndrome
- D. Marfan syndrome (Correct Answer)
Explanation: ***Marfan syndrome***- The **FBN1 gene** (located on chromosome 15) encodes the protein **fibrillin-1**, a major component of the extracellular matrix, deficiency of which leads to the clinical manifestations of Marfan syndrome.- **Fibrillin-1** is integral to the formation of elastic fibers; its defect causes issues in the skeletal, ocular, and cardiovascular systems [1].*Ehlers-Danlos syndrome*- This group of disorders is primarily caused by defects in **collagen synthesis** (e.g., **COL5A1**, **COL3A1**) or processing, leading to joint hypermobility and skin hyperextensibility [2].- It is not typically associated with the **FBN1** mutation.*Homocystinuria*- This disorder is an autosomal recessive metabolic error usually caused by a deficiency of the enzyme **cystathionine beta-synthase** (CBS) [3].- It involves abnormal metabolism of **methionine** and **cysteine**, leading to high levels of **homocysteine**, and is not linked to **FBN1**.*von Hippel-Lindau syndrome*- This is a predisposition syndrome caused by a mutation in the **VHL tumor suppressor gene** (located on chromosome 3).- It predisposes patients to various tumors, including **hemangioblastomas** and **renal cell carcinoma**, and has no association with **FBN1**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 153-154. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 155-156. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 150-151.
Question 565: Acute hemolytic blood transfusion reactions are mediated by which type of hypersensitivity reaction?
- A. Type I
- B. Type III
- C. Type II (Correct Answer)
- D. Type IV
Explanation: ***Type II***- Acute hemolytic transfusion reactions, the most dangerous type, occur when pre-formed recipient antibodies (usually **IgM** against donor ABO antigens) bind to antigens on the surface of transfused red blood cells, leading to their destruction. [1] - This antibody binding activates the **complement cascade** and/or causes **opsonization** and phagocytosis, characteristic features of Type II hypersensitivity (antibody-mediated cytotoxic reaction). [1], [2] *Type I*- Type I hypersensitivity is **IgE-mediated**, responsible for immediate allergic reactions such as anaphylaxis or urticaria, often due to plasma proteins in the donor blood product. [4] - It involves mast cell and basophil degranulation upon antigen binding, leading to the rapid release of mediators like **histamine**.*Type III*- Type III hypersensitivity involves the formation and deposition of circulating **antigen-antibody immune complexes** in tissues, which then activate complement and cause inflammation (e.g., serum sickness). [3] - While some non-hemolytic transfusion reactions may involve immune complexes, the primary mechanism of cell destruction in acute hemolytic reactions is not due to complex deposition.*Type IV*- Type IV hypersensitivity is a **delayed-type reaction** mediated by **T lymphocytes** and macrophages, taking 24-72 hours or more to manifest. - This mechanism is involved in conditions like graft-versus-host disease (GVHD) and contact dermatitis, but it is not the cause of immediate or acute immunologic transfusion reactions involving red cell destruction. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 208-210. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, p. 214. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 172-173. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 212-213.
Pediatrics
4 questionsA 12-year-old child presents with short stature. On evaluation, the bone age is found to be less than the chronological age. There are no dysmorphic features, and the child is otherwise healthy. What is the most likely diagnosis?
A newborn, born to a diabetic mother, presents after 24 hours of life with a blood glucose level of <35 mg/dL. The baby is symptomatic. What is the next best step in management?
A young boy is brought to the clinic for developmental assessment. On examination, he has a prominent epicanthal fold, a single transverse palmar crease, hypotonia, and intellectual disability. Facial features appear flat with upslanting palpebral fissures. What is the most likely diagnosis?
A 10-year-old child weighs 40 kg and presents with mental retardation. On examination, the upper segment to lower segment (US:LS) ratio is 1.1:1. What is the most likely diagnosis?
FMGE 2025 - Pediatrics FMGE Practice Questions and MCQs
Question 561: A 12-year-old child presents with short stature. On evaluation, the bone age is found to be less than the chronological age. There are no dysmorphic features, and the child is otherwise healthy. What is the most likely diagnosis?
- A. Achondroplasia
- B. Chondrodysplasia
- C. Constitutional delay of growth and puberty (Correct Answer)
- D. Familial short stature
Explanation: ***Constitutional delay of growth and puberty*** - This condition is the most common cause of short stature in healthy children, defined by a delayed maturation profile resulting in **bone age significantly less** than the chronological age. - The child is otherwise healthy and lacks dysmorphic features, suggesting a normal eventual final height, albeit with delayed onset of **puberty** and growth spurt. *Familial short stature* - Children with this diagnosis are genetically programmed to be short, leading to a final adult height consistent with their parents' stature. - A key differentiating feature is that the **bone age is commensurate** with the chronological age, which contradicts the finding in this patient. *Achondroplasia* - This is a specific form of **skeletal dysplasia** characterized by marked physical findings, including **rhizomelic short limbs** (shortening of proximal segments) and **macrocephaly**. - The presence of *no dysmorphic features* in this child strongly argues against the diagnosis of achondroplasia. *Chondrodysplasia* - This term encompasses a broad group of disorders involving defects in cartilage and bone development, which typically result in **disproportionate short stature** and specific skeletal abnormalities. - The description of the child being *otherwise healthy* and lacking dysmorphic features makes a significant, underlying generalized skeletal dysplasia highly improbable.
Question 562: A newborn, born to a diabetic mother, presents after 24 hours of life with a blood glucose level of <35 mg/dL. The baby is symptomatic. What is the next best step in management?
- A. Administer IV bolus of Hartmann solution
- B. Start oral feeds and observe
- C. Recheck blood glucose after 20 minutes
- D. Administer IV glucose and recheck blood glucose after 20 minutes (Correct Answer)
Explanation: ***Administer IV glucose and recheck blood glucose after 20 minutes*** - Symptomatic hypoglycemia (blood glucose <40–45 mg/dL, often <35 mg/dL) requires immediate treatment with an **IV dextrose bolus** (typically D10W at 2 mL/kg) to rapidly correct the glucose deficit and prevent **neurological injury**. - After administering the IV bolus, the effectiveness of the treatment must be confirmed by repeating the blood glucose level measurement within 15–30 minutes (recheck after 20 minutes) to ensure target levels are maintained. *Administer IV bolus of Hartmann solution* - **Hartmann solution (Lactated Ringer's)** is an isotonic crystalloid mainly used for volume expansion and contains negligible dextrose, making it ineffective for treating severe, symptomatic **hypoglycemia**. - Using an IV fluid without sufficient glucose will lead to a dangerous delay in restoring adequate **cerebral glucose delivery**. *Recheck blood glucose after 20 minutes* - Since the infant is **symptomatic**, there is an immediate risk of irreversible **neurological damage**; therefore, treatment cannot be delayed for confirmation. - Immediate intervention with **IV dextrose** is mandatory for all symptomatic neonates regardless of the time since the last measurement, followed by a recheck. *Start oral feeds and observe* - Oral feeds are appropriate only for managing **asymptomatic, mild to moderate hypoglycemia** (e.g., in high-risk infants who screen positive but are clinically well). - Given the symptoms and blood glucose <35 mg/dL, relying on slow absorption from oral feeds is inadequate and exposes the infant to the risk of seizures and **brain injury**.
Question 563: A young boy is brought to the clinic for developmental assessment. On examination, he has a prominent epicanthal fold, a single transverse palmar crease, hypotonia, and intellectual disability. Facial features appear flat with upslanting palpebral fissures. What is the most likely diagnosis?
- A. Down syndrome (Correct Answer)
- B. Patau syndrome
- C. Edward syndrome
- D. Fragile X syndrome
Explanation: ***Down syndrome*** (Trisomy 21) is the most likely diagnosis, as the combination of **hypotonia**, **intellectual disability**, **flat facial features**, **upslanting palpebral fissures**, and a **single transverse palmar crease** (Simian crease) are classic findings. The presence of these multiple congenital anomalies suggests a chromosomal abnormality, with Trisomy 21 being the most common cause of intellectual disability associated with these findings. *Patau syndrome* (Trisomy 13) is characterized by severe midline defects such as **cleft lip and palate**, **microphthalmia**, and **polydactyly**, features not mentioned in this presentation. *Edward syndrome* (Trisomy 18) is typically associated with **rocker-bottom feet**, **micrognathia**, and characteristic **clenched hands** with overlapping fingers, making this option less likely. Finally, *Fragile X syndrome* is an X-linked disorder presenting with large ears, a long face, and **macroorchidism** (in post-pubertal males), but lacks the specific facial and palmar crease findings described here.
Question 564: A 10-year-old child weighs 40 kg and presents with mental retardation. On examination, the upper segment to lower segment (US:LS) ratio is 1.1:1. What is the most likely diagnosis?
- A. Achondroplasia
- B. Hypothyroidism
- C. Cretinism (Correct Answer)
- D. Rickets
Explanation: ***Cretinism*** - **Cretinism** (untreated congenital **hypothyroidism**) is the classic cause of the combination of **mental retardation** and **short stature with increased US:LS ratio** in children. - **Mental retardation** is a hallmark feature of cretinism due to the critical role of thyroid hormone in brain development during fetal and early postnatal life. - The **increased US:LS ratio** (1.1:1 at age 10, compared to normal 1.0:1) results from **disproportionate skeletal growth** with delayed bone maturation and relatively shorter lower limbs. - Clinical features include coarse facial features, large tongue, umbilical hernia, prolonged jaundice, hypotonia, and delayed developmental milestones. *Incorrect: Rickets* - **Rickets** (vitamin D deficiency) causes skeletal deformities including bowing of legs, rachitic rosary, and growth retardation with possible increased US:LS ratio. - However, **rickets does NOT cause mental retardation** — it is purely a disorder of bone mineralization and does not affect cognitive development. - The presence of mental retardation in this case rules out rickets as the primary diagnosis. *Incorrect: Achondroplasia* - Achondroplasia causes **rhizomelic dwarfism** with markedly increased US:LS ratio (typically >1.5:1), far more dramatic than the 1.1:1 seen here. - Crucially, **intelligence is normal** in achondroplasia, which contradicts the finding of mental retardation in this case. *Incorrect: Hypothyroidism* - **Acquired juvenile hypothyroidism** (after age 2-3 years) can cause growth failure and mild increase in US:LS ratio. - However, **severe mental retardation is rare** in acquired hypothyroidism because brain development is largely complete by this age. - The term "hypothyroidism" without qualifier typically refers to acquired disease, whereas **cretinism** specifically denotes congenital hypothyroidism with its characteristic neurological sequelae.