USMLE STEP 1 / NBME CBSE
COMPREHENSIVE MEDICAL
EXAMINATION 2026/2027 QUESTIONS
AND ANSWERS
1. A 25-year-old male presents with recurrent episodes of dark urine, especially in the
morning. Labs show hemolytic anemia, leukopenia, and thrombocytopenia. Flow cytometry
reveals a deficiency of CD55 and CD59 on red blood cells. What is the most likely underlying
mechanism?
A. Autoantibodies against RBC membrane proteins
B. Mutation in the PIGA gene leading to impaired GPI anchor synthesis
C. Deficiency of glucose-6-phosphate dehydrogenase
D. Defect in the spectrin and ankyrin proteins
Answer: B
Conceptual Explanation: Paroxysmal nocturnal hemoglobinuria (PNH) is caused by an
acquired mutation in the PIGA gene, which leads to a loss of GPI-anchored proteins like
CD55 and CD59, making RBCs susceptible to complement-mediated lysis.
,2. A 45-year-old female with a history of systemic lupus erythematosus (SLE) presents with
swelling of the legs and foamy urine. A renal biopsy shows a ‘spike and dome’ appearance on
electron microscopy and subepithelial deposits. What is the diagnosis?
A. Minimal change disease
B. Membranoproliferative glomerulonephritis
C. Focal segmental glomerulosclerosis
D. Membranous nephropathy
Answer: D
Conceptual Explanation: Membranous nephropathy is a common cause of nephrotic
syndrome in adults and can be associated with SLE (class V lupus nephritis). It is
characterized by subepithelial immune complex deposits and basement membrane
thickening (spike and dome).
3. A 60-year-old male with chronic alcoholism presents with confusion, ataxia, and
ophthalmoplegia. Which vitamin deficiency is the most likely cause of these symptoms?
A. Vitamin B12 (Cobalamin)
B. Vitamin B6 (Pyridoxine)
C. Vitamin B3 (Niacin)
D. Vitamin B1 (Thiamine)
E. Vitamin B9 (Folate)
, Answer: D
Conceptual Explanation: Wernicke encephalopathy is characterized by the triad of
confusion, ataxia, and ophthalmoplegia, resulting from thiamine (B1) deficiency, commonly
seen in chronic alcohol use.
4. A 10-year-old boy presents with sudden onset of abdominal pain and dark-colored urine
after being treated with nitrofurantoin for a urinary tract infection. Peripheral blood smear
shows bite cells and Heinz bodies. What is the most likely diagnosis?
A. Hereditary spherocytosis
B. Glucose-6-phosphate dehydrogenase deficiency
C. Sickle cell anemia
D. Pyruvate kinase deficiency
Answer: B
Conceptual Explanation: G6PD deficiency causes episodic hemolytic anemia induced by
oxidative stress (e.g., nitrofurantoin, fava beans, infection). Heinz bodies (denatured
hemoglobin) and bite cells (formed by splenic macrophages) are characteristic.
5. A 30-year-old woman presents with palpitations, weight loss, and heat intolerance.
Physical exam shows a diffuse, non-tender enlargement of the thyroid gland and
exophthalmos. Which of the following is the most likely mechanism?
A. TSH-secreting pituitary adenoma
B. Antibodies against the TSH receptor
COMPREHENSIVE MEDICAL
EXAMINATION 2026/2027 QUESTIONS
AND ANSWERS
1. A 25-year-old male presents with recurrent episodes of dark urine, especially in the
morning. Labs show hemolytic anemia, leukopenia, and thrombocytopenia. Flow cytometry
reveals a deficiency of CD55 and CD59 on red blood cells. What is the most likely underlying
mechanism?
A. Autoantibodies against RBC membrane proteins
B. Mutation in the PIGA gene leading to impaired GPI anchor synthesis
C. Deficiency of glucose-6-phosphate dehydrogenase
D. Defect in the spectrin and ankyrin proteins
Answer: B
Conceptual Explanation: Paroxysmal nocturnal hemoglobinuria (PNH) is caused by an
acquired mutation in the PIGA gene, which leads to a loss of GPI-anchored proteins like
CD55 and CD59, making RBCs susceptible to complement-mediated lysis.
,2. A 45-year-old female with a history of systemic lupus erythematosus (SLE) presents with
swelling of the legs and foamy urine. A renal biopsy shows a ‘spike and dome’ appearance on
electron microscopy and subepithelial deposits. What is the diagnosis?
A. Minimal change disease
B. Membranoproliferative glomerulonephritis
C. Focal segmental glomerulosclerosis
D. Membranous nephropathy
Answer: D
Conceptual Explanation: Membranous nephropathy is a common cause of nephrotic
syndrome in adults and can be associated with SLE (class V lupus nephritis). It is
characterized by subepithelial immune complex deposits and basement membrane
thickening (spike and dome).
3. A 60-year-old male with chronic alcoholism presents with confusion, ataxia, and
ophthalmoplegia. Which vitamin deficiency is the most likely cause of these symptoms?
A. Vitamin B12 (Cobalamin)
B. Vitamin B6 (Pyridoxine)
C. Vitamin B3 (Niacin)
D. Vitamin B1 (Thiamine)
E. Vitamin B9 (Folate)
, Answer: D
Conceptual Explanation: Wernicke encephalopathy is characterized by the triad of
confusion, ataxia, and ophthalmoplegia, resulting from thiamine (B1) deficiency, commonly
seen in chronic alcohol use.
4. A 10-year-old boy presents with sudden onset of abdominal pain and dark-colored urine
after being treated with nitrofurantoin for a urinary tract infection. Peripheral blood smear
shows bite cells and Heinz bodies. What is the most likely diagnosis?
A. Hereditary spherocytosis
B. Glucose-6-phosphate dehydrogenase deficiency
C. Sickle cell anemia
D. Pyruvate kinase deficiency
Answer: B
Conceptual Explanation: G6PD deficiency causes episodic hemolytic anemia induced by
oxidative stress (e.g., nitrofurantoin, fava beans, infection). Heinz bodies (denatured
hemoglobin) and bite cells (formed by splenic macrophages) are characteristic.
5. A 30-year-old woman presents with palpitations, weight loss, and heat intolerance.
Physical exam shows a diffuse, non-tender enlargement of the thyroid gland and
exophthalmos. Which of the following is the most likely mechanism?
A. TSH-secreting pituitary adenoma
B. Antibodies against the TSH receptor
