NBME CBSE Actual Test Questions and Answers 2026/2027 (Quiz Bank
with All the Correct Answers) (USMLE Step 1) Medical Examination
Actual Exam 2026/2027 | Complete Exam-Style Questions with Detailed
Rationales | Graded A+
Biochemistry, Molecular Biology, and Genetics
Q1: A 4-year-old boy presents with developmental delay and self-mutilating behavior,
including biting his lips. Serum uric acid is elevated. Which enzyme is deficient?
A. Adenosine deaminase
B. Hypoxanthine-guanine phosphoribosyltransferase [CORRECT]
C. Phenylalanine hydroxylase
D. Glucose-6-phosphatase
Correct Answer: B
Rationale: The best answer is hypoxanthine-guanine phosphoribosyltransferase deficiency,
which causes Lesch-Nyhan syndrome, characterized by hyperuricemia, developmental
delay, and self-mutilation due to impaired purine salvage.
Q2: A 19-year-old tall, thin male presents with a spontaneous pneumothorax and a systolic
murmur at the apex. Genetic testing reveals a mutation in the FBN1 gene. Which of the
following is the most likely underlying defect?
A. Defective type I collagen synthesis
B. Defective fibrillin-1 glycoprotein [CORRECT]
C. Defective dystrophin protein
D. Defective elastin cross-linking
Correct Answer: B
Rationale: This choice is correct because Marfan syndrome is caused by a mutation in the
FBN1 gene, leading to defective fibrillin-1, which manifests as tall stature, lens dislocation,
and aortic root dilation or mitral valve prolapse.
Q3: A newborn presents with severe hypotonia, seizures, and hepatomegaly. Laboratory
studies show elevated very-long-chain fatty acids. Which cellular organelle is most likely
defective?
A. Mitochondria
B. Lysosomes
C. Peroxisomes [CORRECT]
D. Golgi apparatus
Correct Answer: C
Rationale: The best answer is peroxisomes, as Zellweger syndrome is a peroxisomal
biogenesis disorder characterized by the accumulation of very-long-chain fatty acids, leading
to severe neurologic and hepatic dysfunction.
,Q4: A 6-month-old infant presents with fasting hypoglycemia, lactic acidosis, and
hepatomegaly. Liver biopsy shows excess glycogen with normal structure. Which enzyme is
most likely deficient?
A. Glycogen phosphorylase
B. Glucose-6-phosphatase [CORRECT]
C. Lysosomal acid alpha-1,4-glucosidase
D. Branching enzyme
Correct Answer: B
Rationale: This aligns with von Gierke disease (Glycogen storage disease type I), where
glucose-6-phosphatase deficiency prevents the release of free glucose from the liver,
causing severe fasting hypoglycemia and lactic acidosis.
Q5: A 65-year-old vegan presents with fatigue, paresthesias, and a macrocytic anemia.
Laboratory studies show elevated methylmalonic acid and homocysteine levels. Which
vitamin deficiency is most likely?
A. Folate (Vitamin B9)
B. Vitamin B12 (Cobalamin) [CORRECT]
C. Vitamin B6 (Pyridoxine)
D. Vitamin B1 (Thiamine)
Correct Answer: B
Rationale: The best answer is vitamin B12 deficiency, which uniquely causes elevated
methylmalonic acid and homocysteine, leading to macrocytic anemia and subacute
combined degeneration of the spinal cord.
Q6: A child presents with multiple fractures after minor trauma, blue sclerae, and hearing
loss. Which of the following molecular defects is the most likely cause?
A. Defective type I collagen synthesis [CORRECT]
B. Defective type II collagen synthesis
C. Defective type IV collagen synthesis
D. Defective fibrillin-1
Correct Answer: A
Rationale: This matches the principle that osteogenesis imperfecta is most commonly
caused by autosomal dominant mutations in COL1A1 or COL1A2, leading to defective type I
collagen synthesis and resulting in brittle bones and blue sclerae.
Q7: A 25-year-old African American male develops jaundice and dark urine after taking
primaquine for malaria prophylaxis. A peripheral blood smear shows bite cells and Heinz
bodies. Which enzyme is deficient?
A. Pyruvate kinase
B. Glucose-6-phosphate dehydrogenase [CORRECT]
C. Hexosaminidase A
D. Sphingomyelinase
Correct Answer: B
Rationale: The best answer is glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-
linked recessive disorder where oxidative stress from drugs like primaquine causes
hemoglobin denaturation (Heinz bodies) and subsequent hemolysis.
, Q8: A 1-year-old Ashkenazi Jewish child presents with progressive neurodegeneration, a
cherry-red spot on the macula, and an exaggerated startle response. No
hepatosplenomegaly is noted. Which enzyme is deficient?
A. Glucocerebrosidase
B. Hexosaminidase A [CORRECT]
C. Sphingomyelinase
D. Alpha-galactosidase A
Correct Answer: B
Rationale: This choice is correct because Tay-Sachs disease is caused by hexosaminidase A
deficiency, leading to GM2 ganglioside accumulation, presenting with neurodegeneration
and a macular cherry-red spot without hepatosplenomegaly.
Q9: A newborn fails the routine metabolic screening. Further testing reveals elevated
phenylalanine levels and a musty body odor. Which of the following is the most appropriate
initial treatment?
A. Supplementation with tetrahydrobiopterin
B. Dietary restriction of phenylalanine [CORRECT]
C. Administration of nitisinone
D. Bone marrow transplantation
Correct Answer: B
Rationale: The best answer is dietary restriction of phenylalanine, as phenylketonuria (PKU)
is caused by phenylalanine hydroxylase deficiency, and early dietary intervention prevents
severe intellectual disability.
Q10: A 30-year-old male presents with tendon xanthomas and a family history of early
myocardial infarction. Laboratory studies show markedly elevated LDL cholesterol. Which
defect is most likely responsible?
A. Defective apolipoprotein B-100
B. Defective LDL receptor [CORRECT]
C. Defective lipoprotein lipase
D. Defective apolipoprotein E
Correct Answer: B
Rationale: This aligns with familial hypercholesterolemia, which is most commonly caused
by an autosomal dominant defect in the LDL receptor, leading to decreased LDL clearance
and severely elevated serum cholesterol levels.
Q11: A 40-year-old man presents with dark urine that turns black upon standing and bluish-
black discoloration of his ear cartilage. Which enzyme is deficient?
A. Homogentisate oxidase [CORRECT]
B. Phenylalanine hydroxylase
C. Tyrosinase
D. Branched-chain ketoacid dehydrogenase
Correct Answer: A
Rationale: The best answer is homogentisate oxidase deficiency, which causes alkaptonuria,
characterized by the accumulation of homogentisic acid that oxidizes and polymerizes to
cause dark urine and ochronosis (bluish-black cartilage).
with All the Correct Answers) (USMLE Step 1) Medical Examination
Actual Exam 2026/2027 | Complete Exam-Style Questions with Detailed
Rationales | Graded A+
Biochemistry, Molecular Biology, and Genetics
Q1: A 4-year-old boy presents with developmental delay and self-mutilating behavior,
including biting his lips. Serum uric acid is elevated. Which enzyme is deficient?
A. Adenosine deaminase
B. Hypoxanthine-guanine phosphoribosyltransferase [CORRECT]
C. Phenylalanine hydroxylase
D. Glucose-6-phosphatase
Correct Answer: B
Rationale: The best answer is hypoxanthine-guanine phosphoribosyltransferase deficiency,
which causes Lesch-Nyhan syndrome, characterized by hyperuricemia, developmental
delay, and self-mutilation due to impaired purine salvage.
Q2: A 19-year-old tall, thin male presents with a spontaneous pneumothorax and a systolic
murmur at the apex. Genetic testing reveals a mutation in the FBN1 gene. Which of the
following is the most likely underlying defect?
A. Defective type I collagen synthesis
B. Defective fibrillin-1 glycoprotein [CORRECT]
C. Defective dystrophin protein
D. Defective elastin cross-linking
Correct Answer: B
Rationale: This choice is correct because Marfan syndrome is caused by a mutation in the
FBN1 gene, leading to defective fibrillin-1, which manifests as tall stature, lens dislocation,
and aortic root dilation or mitral valve prolapse.
Q3: A newborn presents with severe hypotonia, seizures, and hepatomegaly. Laboratory
studies show elevated very-long-chain fatty acids. Which cellular organelle is most likely
defective?
A. Mitochondria
B. Lysosomes
C. Peroxisomes [CORRECT]
D. Golgi apparatus
Correct Answer: C
Rationale: The best answer is peroxisomes, as Zellweger syndrome is a peroxisomal
biogenesis disorder characterized by the accumulation of very-long-chain fatty acids, leading
to severe neurologic and hepatic dysfunction.
,Q4: A 6-month-old infant presents with fasting hypoglycemia, lactic acidosis, and
hepatomegaly. Liver biopsy shows excess glycogen with normal structure. Which enzyme is
most likely deficient?
A. Glycogen phosphorylase
B. Glucose-6-phosphatase [CORRECT]
C. Lysosomal acid alpha-1,4-glucosidase
D. Branching enzyme
Correct Answer: B
Rationale: This aligns with von Gierke disease (Glycogen storage disease type I), where
glucose-6-phosphatase deficiency prevents the release of free glucose from the liver,
causing severe fasting hypoglycemia and lactic acidosis.
Q5: A 65-year-old vegan presents with fatigue, paresthesias, and a macrocytic anemia.
Laboratory studies show elevated methylmalonic acid and homocysteine levels. Which
vitamin deficiency is most likely?
A. Folate (Vitamin B9)
B. Vitamin B12 (Cobalamin) [CORRECT]
C. Vitamin B6 (Pyridoxine)
D. Vitamin B1 (Thiamine)
Correct Answer: B
Rationale: The best answer is vitamin B12 deficiency, which uniquely causes elevated
methylmalonic acid and homocysteine, leading to macrocytic anemia and subacute
combined degeneration of the spinal cord.
Q6: A child presents with multiple fractures after minor trauma, blue sclerae, and hearing
loss. Which of the following molecular defects is the most likely cause?
A. Defective type I collagen synthesis [CORRECT]
B. Defective type II collagen synthesis
C. Defective type IV collagen synthesis
D. Defective fibrillin-1
Correct Answer: A
Rationale: This matches the principle that osteogenesis imperfecta is most commonly
caused by autosomal dominant mutations in COL1A1 or COL1A2, leading to defective type I
collagen synthesis and resulting in brittle bones and blue sclerae.
Q7: A 25-year-old African American male develops jaundice and dark urine after taking
primaquine for malaria prophylaxis. A peripheral blood smear shows bite cells and Heinz
bodies. Which enzyme is deficient?
A. Pyruvate kinase
B. Glucose-6-phosphate dehydrogenase [CORRECT]
C. Hexosaminidase A
D. Sphingomyelinase
Correct Answer: B
Rationale: The best answer is glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-
linked recessive disorder where oxidative stress from drugs like primaquine causes
hemoglobin denaturation (Heinz bodies) and subsequent hemolysis.
, Q8: A 1-year-old Ashkenazi Jewish child presents with progressive neurodegeneration, a
cherry-red spot on the macula, and an exaggerated startle response. No
hepatosplenomegaly is noted. Which enzyme is deficient?
A. Glucocerebrosidase
B. Hexosaminidase A [CORRECT]
C. Sphingomyelinase
D. Alpha-galactosidase A
Correct Answer: B
Rationale: This choice is correct because Tay-Sachs disease is caused by hexosaminidase A
deficiency, leading to GM2 ganglioside accumulation, presenting with neurodegeneration
and a macular cherry-red spot without hepatosplenomegaly.
Q9: A newborn fails the routine metabolic screening. Further testing reveals elevated
phenylalanine levels and a musty body odor. Which of the following is the most appropriate
initial treatment?
A. Supplementation with tetrahydrobiopterin
B. Dietary restriction of phenylalanine [CORRECT]
C. Administration of nitisinone
D. Bone marrow transplantation
Correct Answer: B
Rationale: The best answer is dietary restriction of phenylalanine, as phenylketonuria (PKU)
is caused by phenylalanine hydroxylase deficiency, and early dietary intervention prevents
severe intellectual disability.
Q10: A 30-year-old male presents with tendon xanthomas and a family history of early
myocardial infarction. Laboratory studies show markedly elevated LDL cholesterol. Which
defect is most likely responsible?
A. Defective apolipoprotein B-100
B. Defective LDL receptor [CORRECT]
C. Defective lipoprotein lipase
D. Defective apolipoprotein E
Correct Answer: B
Rationale: This aligns with familial hypercholesterolemia, which is most commonly caused
by an autosomal dominant defect in the LDL receptor, leading to decreased LDL clearance
and severely elevated serum cholesterol levels.
Q11: A 40-year-old man presents with dark urine that turns black upon standing and bluish-
black discoloration of his ear cartilage. Which enzyme is deficient?
A. Homogentisate oxidase [CORRECT]
B. Phenylalanine hydroxylase
C. Tyrosinase
D. Branched-chain ketoacid dehydrogenase
Correct Answer: A
Rationale: The best answer is homogentisate oxidase deficiency, which causes alkaptonuria,
characterized by the accumulation of homogentisic acid that oxidizes and polymerizes to
cause dark urine and ochronosis (bluish-black cartilage).
