NBME CBSE Exam 2026-2027 – Complete Basic Science Review (Clinical Vignettes with Verified,
Exams of Medical Sciences Comprehensive Assessment | 2026-2027 | 100 questions | 100%
VERIFIED
Introduction
This comprehensive basic science assessment integrates Biochemistry and Molecular Biology, Cellular Biology
and Genetics, Immunology and Microbiology, Pharmacology and Autonomics, Cardiovascular and Respiratory
Physiology, Renal and Gastrointestinal Physiology, Endocrinology and Reproductive Physiology, and
Neurosciences and Behavioral Sciences. Clinical vignettes emphasize mechanisms, interpretation, and
evidence-informed clinical execution, supporting USMLE Step 1 preparation and durable medical-science
reasoning.
1. A newborn develops severe fasting hypoglycemia, lactic acidosis, and hepatomegaly. Which enzyme
deficiency is most likely?
A. Glucose-6-phosphatase
B. Branched-chain alpha-ketoacid dehydrogenase
C. Phenylalanine hydroxylase
D. Medium-chain acyl-CoA dehydrogenase
Rationale: Glucose-6-phosphatase deficiency prevents release of free glucose from glycogenolysis and
gluconeogenesis, causing fasting hypoglycemia and hepatomegaly.
2. A patient has muscle cramps after intense exertion and dark urine. Which defect best explains this
presentation?
A. Lysosomal acid alpha-glucosidase deficiency
B. Glucose-6-phosphatase deficiency
C. Muscle glycogen phosphorylase deficiency
D. Pyruvate dehydrogenase excess
Rationale: McArdle disease impairs muscle glycogen breakdown, causing exertional cramps and myoglobinuria; the
other defects have different organ patterns.
3. A child with developmental delay has a musty body odor and eczema. Which metabolic abnormality is
expected?
A. Accumulation of phenylalanine
B. Accumulation of homogentisic acid
C. Deficiency of branched-chain amino acids
D. Excess methylmalonic acid only
Rationale: Phenylalanine hydroxylase deficiency causes phenylalanine accumulation, intellectual disability, eczema,
and a musty odor.
4. A patient with hereditary spherocytosis has chronic hemolysis. Which red-cell abnormality is most likely?
A. Defective beta-globin synthesis
B. Reduced membrane spectrin stability
C. Absent glucose-6-phosphate dehydrogenase
D. Excess fetal hemoglobin
Rationale: Membrane protein defects reduce red-cell deformability and cause splenic sequestration; the alternatives
cause other hemolytic or microcytic disorders.
5. A tumor suppressor normally halts the cell cycle after DNA damage. Loss of which protein removes this
checkpoint?
A. RAS
, B. Cyclin D
C. Telomerase
D. p53
Rationale: p53 induces cell-cycle arrest or apoptosis after damage; RAS and cyclin D promote proliferation, while
telomerase supports replicative capacity.
6. A researcher measures gene expression by converting RNA to complementary DNA, then amplifying a target
sequence. Which method is being used?
A. Southern blotting
B. Reverse-transcription polymerase chain reaction
C. Fluorescence in situ hybridization
D. Western blotting
Rationale: Reverse transcription converts RNA to cDNA before PCR amplification; the other techniques detect DNA
location, DNA fragments, or proteins.
7. A patient with severe diarrhea has metabolic acidosis. Which respiratory response is expected?
A. Decreased ventilation with increased arterial carbon dioxide
B. Decreased bicarbonate excretion by the lungs
C. Increased arterial carbon dioxide from hypoventilation
D. Increased alveolar ventilation with decreased arterial carbon dioxide
Rationale: Metabolic acidosis stimulates hyperventilation, lowering carbon dioxide as compensation; lungs do not
excrete bicarbonate.
8. Which vitamin deficiency most directly impairs hydroxylation of collagen proline and lysine?
A. Vitamin K
B. Vitamin C
C. Vitamin B12
D. Vitamin D
Rationale: Vitamin C is required for collagen hydroxylation; deficiency produces impaired wound healing and
bleeding gums.
9. A patient has neurologic symptoms and macrocytosis despite adequate folate. Which reaction is impaired in
vitamin B12 deficiency?
A. Conversion of pyruvate to acetyl-CoA
B. Conversion of glucose-6-phosphate to fructose-6-phosphate
C. Conversion of methylmalonyl-CoA to succinyl-CoA
D. Conversion of tyrosine to dopamine
Rationale: B12 is required for methylmalonyl-CoA mutase and methionine synthase; methylmalonic acid accumulates
and neurologic injury develops.
10. A competitive inhibitor is added to an enzyme-catalyzed reaction. Which kinetic change occurs?
A. Decreased Km with decreased Vmax
B. Increased apparent Km with unchanged Vmax
C. Unchanged Km with decreased Vmax
D. Increased Vmax with unchanged Km
Rationale: Competitive inhibition can be overcome by substrate, increasing apparent Km while leaving Vmax
unchanged.
11. A child has recurrent infections and severe diarrhea due to impaired intestinal absorption of neutral amino
acids. Which disorder is likely?
A. Hartnup disease
B. Cystinuria
C. Alkaptonuria
D. Maple syrup urine disease
, Rationale: Hartnup disease is a neutral amino-acid transport defect causing pellagra-like findings; cystinuria affects
dibasic amino acids and stones.
12. A patient with alcohol use disorder has confusion, ataxia, and ophthalmoplegia. Which enzyme reaction is
impaired?
A. DNA thymidine synthesis only
B. Collagen cross-linking only
C. Urea-cycle transport only
D. Pyruvate dehydrogenase and transketolase reactions
Rationale: Thiamine deficiency impairs transketolase and pyruvate dehydrogenase, producing Wernicke findings and
lactic acidosis.
13. A patient has jaundice, anemia, and increased unconjugated bilirubin after taking an oxidant drug. Which
defect is most likely?
A. Glucose-6-phosphate dehydrogenase deficiency
B. UDP-glucuronosyltransferase excess
C. Pyruvate kinase excess
D. Alpha-fetoprotein deficiency
Rationale: G6PD deficiency lowers NADPH and reduced glutathione, making red cells vulnerable to oxidative
hemolysis.
14. A child has recurrent sinopulmonary infections, hypocalcemia, and a conotruncal cardiac defect. Which
developmental abnormality is likely?
A. Trisomy 21
B. 22q11.2 deletion affecting pharyngeal pouch development
C. FMR1 expansion
D. DNA mismatch repair mutation
Rationale: The 22q11.2 deletion disrupts thymic and parathyroid development and is associated with conotruncal
defects.
15. A woman with a balanced reciprocal translocation has repeated miscarriages. Why can this occur?
A. Meiotic segregation can produce unbalanced gametes
B. All offspring must inherit the balanced translocation
C. The translocation always causes maternal infertility
D. The abnormality prevents DNA replication in every cell
Rationale: Balanced carriers may be healthy but can form gametes with duplications or deletions after abnormal
segregation.
16. A child has intellectual disability, long face, and enlarged testes. Which molecular mechanism is
responsible?
A. CAG expansion in the HTT gene
B. Deletion of the dystrophin gene
C. CGG repeat expansion with methylation of the FMR1 promoter
D. Imprinting defect on chromosome 15
Rationale: Fragile X syndrome results from a methylated FMR1 promoter after CGG expansion; the alternatives
describe other disorders.
17. A biopsy shows cells with abundant eosinophilic cytoplasm and shrunken nuclei. Which process is
occurring?
A. Apoptosis
B. Coagulative necrosis
C. Liquefactive necrosis
D. Fat necrosis
Exams of Medical Sciences Comprehensive Assessment | 2026-2027 | 100 questions | 100%
VERIFIED
Introduction
This comprehensive basic science assessment integrates Biochemistry and Molecular Biology, Cellular Biology
and Genetics, Immunology and Microbiology, Pharmacology and Autonomics, Cardiovascular and Respiratory
Physiology, Renal and Gastrointestinal Physiology, Endocrinology and Reproductive Physiology, and
Neurosciences and Behavioral Sciences. Clinical vignettes emphasize mechanisms, interpretation, and
evidence-informed clinical execution, supporting USMLE Step 1 preparation and durable medical-science
reasoning.
1. A newborn develops severe fasting hypoglycemia, lactic acidosis, and hepatomegaly. Which enzyme
deficiency is most likely?
A. Glucose-6-phosphatase
B. Branched-chain alpha-ketoacid dehydrogenase
C. Phenylalanine hydroxylase
D. Medium-chain acyl-CoA dehydrogenase
Rationale: Glucose-6-phosphatase deficiency prevents release of free glucose from glycogenolysis and
gluconeogenesis, causing fasting hypoglycemia and hepatomegaly.
2. A patient has muscle cramps after intense exertion and dark urine. Which defect best explains this
presentation?
A. Lysosomal acid alpha-glucosidase deficiency
B. Glucose-6-phosphatase deficiency
C. Muscle glycogen phosphorylase deficiency
D. Pyruvate dehydrogenase excess
Rationale: McArdle disease impairs muscle glycogen breakdown, causing exertional cramps and myoglobinuria; the
other defects have different organ patterns.
3. A child with developmental delay has a musty body odor and eczema. Which metabolic abnormality is
expected?
A. Accumulation of phenylalanine
B. Accumulation of homogentisic acid
C. Deficiency of branched-chain amino acids
D. Excess methylmalonic acid only
Rationale: Phenylalanine hydroxylase deficiency causes phenylalanine accumulation, intellectual disability, eczema,
and a musty odor.
4. A patient with hereditary spherocytosis has chronic hemolysis. Which red-cell abnormality is most likely?
A. Defective beta-globin synthesis
B. Reduced membrane spectrin stability
C. Absent glucose-6-phosphate dehydrogenase
D. Excess fetal hemoglobin
Rationale: Membrane protein defects reduce red-cell deformability and cause splenic sequestration; the alternatives
cause other hemolytic or microcytic disorders.
5. A tumor suppressor normally halts the cell cycle after DNA damage. Loss of which protein removes this
checkpoint?
A. RAS
, B. Cyclin D
C. Telomerase
D. p53
Rationale: p53 induces cell-cycle arrest or apoptosis after damage; RAS and cyclin D promote proliferation, while
telomerase supports replicative capacity.
6. A researcher measures gene expression by converting RNA to complementary DNA, then amplifying a target
sequence. Which method is being used?
A. Southern blotting
B. Reverse-transcription polymerase chain reaction
C. Fluorescence in situ hybridization
D. Western blotting
Rationale: Reverse transcription converts RNA to cDNA before PCR amplification; the other techniques detect DNA
location, DNA fragments, or proteins.
7. A patient with severe diarrhea has metabolic acidosis. Which respiratory response is expected?
A. Decreased ventilation with increased arterial carbon dioxide
B. Decreased bicarbonate excretion by the lungs
C. Increased arterial carbon dioxide from hypoventilation
D. Increased alveolar ventilation with decreased arterial carbon dioxide
Rationale: Metabolic acidosis stimulates hyperventilation, lowering carbon dioxide as compensation; lungs do not
excrete bicarbonate.
8. Which vitamin deficiency most directly impairs hydroxylation of collagen proline and lysine?
A. Vitamin K
B. Vitamin C
C. Vitamin B12
D. Vitamin D
Rationale: Vitamin C is required for collagen hydroxylation; deficiency produces impaired wound healing and
bleeding gums.
9. A patient has neurologic symptoms and macrocytosis despite adequate folate. Which reaction is impaired in
vitamin B12 deficiency?
A. Conversion of pyruvate to acetyl-CoA
B. Conversion of glucose-6-phosphate to fructose-6-phosphate
C. Conversion of methylmalonyl-CoA to succinyl-CoA
D. Conversion of tyrosine to dopamine
Rationale: B12 is required for methylmalonyl-CoA mutase and methionine synthase; methylmalonic acid accumulates
and neurologic injury develops.
10. A competitive inhibitor is added to an enzyme-catalyzed reaction. Which kinetic change occurs?
A. Decreased Km with decreased Vmax
B. Increased apparent Km with unchanged Vmax
C. Unchanged Km with decreased Vmax
D. Increased Vmax with unchanged Km
Rationale: Competitive inhibition can be overcome by substrate, increasing apparent Km while leaving Vmax
unchanged.
11. A child has recurrent infections and severe diarrhea due to impaired intestinal absorption of neutral amino
acids. Which disorder is likely?
A. Hartnup disease
B. Cystinuria
C. Alkaptonuria
D. Maple syrup urine disease
, Rationale: Hartnup disease is a neutral amino-acid transport defect causing pellagra-like findings; cystinuria affects
dibasic amino acids and stones.
12. A patient with alcohol use disorder has confusion, ataxia, and ophthalmoplegia. Which enzyme reaction is
impaired?
A. DNA thymidine synthesis only
B. Collagen cross-linking only
C. Urea-cycle transport only
D. Pyruvate dehydrogenase and transketolase reactions
Rationale: Thiamine deficiency impairs transketolase and pyruvate dehydrogenase, producing Wernicke findings and
lactic acidosis.
13. A patient has jaundice, anemia, and increased unconjugated bilirubin after taking an oxidant drug. Which
defect is most likely?
A. Glucose-6-phosphate dehydrogenase deficiency
B. UDP-glucuronosyltransferase excess
C. Pyruvate kinase excess
D. Alpha-fetoprotein deficiency
Rationale: G6PD deficiency lowers NADPH and reduced glutathione, making red cells vulnerable to oxidative
hemolysis.
14. A child has recurrent sinopulmonary infections, hypocalcemia, and a conotruncal cardiac defect. Which
developmental abnormality is likely?
A. Trisomy 21
B. 22q11.2 deletion affecting pharyngeal pouch development
C. FMR1 expansion
D. DNA mismatch repair mutation
Rationale: The 22q11.2 deletion disrupts thymic and parathyroid development and is associated with conotruncal
defects.
15. A woman with a balanced reciprocal translocation has repeated miscarriages. Why can this occur?
A. Meiotic segregation can produce unbalanced gametes
B. All offspring must inherit the balanced translocation
C. The translocation always causes maternal infertility
D. The abnormality prevents DNA replication in every cell
Rationale: Balanced carriers may be healthy but can form gametes with duplications or deletions after abnormal
segregation.
16. A child has intellectual disability, long face, and enlarged testes. Which molecular mechanism is
responsible?
A. CAG expansion in the HTT gene
B. Deletion of the dystrophin gene
C. CGG repeat expansion with methylation of the FMR1 promoter
D. Imprinting defect on chromosome 15
Rationale: Fragile X syndrome results from a methylated FMR1 promoter after CGG expansion; the alternatives
describe other disorders.
17. A biopsy shows cells with abundant eosinophilic cytoplasm and shrunken nuclei. Which process is
occurring?
A. Apoptosis
B. Coagulative necrosis
C. Liquefactive necrosis
D. Fat necrosis
