NBME CBSE REAL EXAM 200 QUESTIONS 2026/2027 |
Complete Exam with Answers | USMLE Step 1 Medical
Examination | Pass Guaranteed - A+ Graded
[Section 1: General Principles (Biochemistry, Molecular Biology, Cell
Biology, Genetics) (Q1-35)]
Question 1
A 4-year-old boy is brought to the pediatrician with developmental delay, seizures, and a
musty odor to his urine. His mother reports that he has fair skin and light-colored eyes
compared to family members. Laboratory studies show elevated serum phenylalanine.
Which enzyme deficiency is responsible for this condition?
A. Homogentisate oxidase
B. Phenylalanine hydroxylase
C. Tyrosine kinase
D. Dihydropteridine reductase
Correct Answer: B
B. Phenylalanine hydroxylase [CORRECT]
Rationale: Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase,
which converts phenylalanine to tyrosine. Classic features include intellectual disability,
seizures, fair skin/light hair (due to impaired melanin synthesis from tyrosine
deficiency), and musty/mousy urine odor. Homogentisate oxidase deficiency causes
alkaptonuria (dark urine, ochronosis). Tyrosine kinase is a signaling enzyme unrelated.
,Dihydropteridine reductase deficiency causes a rare variant of hyperphenylalaninemia
but lacks the classic presentation described. (NBME: Biochemistry - Inborn Errors of
Metabolism)
Question 2
A 45-year-old man with chronic alcoholism presents with confusion, ataxia, and
ophthalmoplegia. He is diagnosed with Wernicke encephalopathy. Which vitamin
deficiency is responsible, and what is the biochemical role of this vitamin?
A. Vitamin B12; cofactor for methionine synthase and methylmalonyl-CoA mutase
B. Thiamine (B1); cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase
C. Folate; cofactor for one-carbon transfer reactions in nucleotide synthesis
D. Niacin (B3); component of NAD⁺ and NADP⁺ in redox reactions
Correct Answer: B
B. Thiamine (B1); cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase [CORRECT]
Rationale: Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia) is caused by
thiamine deficiency, common in alcoholism. Thiamine pyrophosphate (TPP) is a
cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase
(pentose phosphate pathway). Vitamin B12 deficiency causes megaloblastic anemia
and subacute combined degeneration. Folate deficiency causes megaloblastic anemia
without neurologic deficits. Niacin deficiency causes pellagra (3 Ds: dermatitis, diarrhea,
dementia). (NBME: Biochemistry - Vitamins)
Question 3
,A researcher is studying a cell line that cannot synthesize purines de novo. The cells are
able to grow when hypoxanthine and thymidine are added to the culture medium. Which
enzyme deficiency is most likely present in these cells?
A. Dihydrofolate reductase
B. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
C. Adenosine deaminase
D. An enzyme in the de novo purine synthesis pathway
Correct Answer: D
D. An enzyme in the de novo purine synthesis pathway [CORRECT]
Rationale: The ability to grow with hypoxanthine (purine salvage) and thymidine
(pyrimidine salvage) indicates the cells can utilize salvage pathways but cannot perform
de novo synthesis. This is the basis of HAT medium selection in hybridoma technology.
HGPRT deficiency (Option B) would prevent hypoxanthine utilization (Lesch-Nyhan
syndrome). Dihydrofolate reductase deficiency affects both pathways. Adenosine
deaminase deficiency causes SCID. (NBME: Molecular Biology - Purine Metabolism)
Question 4
A 2-year-old girl presents with hepatomegaly, fasting hypoglycemia, and lactic acidosis.
A liver biopsy shows glycogen accumulation with normal structure. Which enzyme
deficiency is most likely?
A. Glucose-6-phosphatase
B. Branching enzyme (α-1,6-glucosidase)
C. Acid maltase (α-1,4-glucosidase)
D. Muscle phosphorylase
Correct Answer: A
, A. Glucose-6-phosphatase [CORRECT]
Rationale: Von Gierke disease (Type I glycogen storage disease) is caused by
glucose-6-phosphatase deficiency, presenting with severe fasting hypoglycemia, lactic
acidosis, hyperuricemia, hepatomegaly, and glycogen accumulation with normal
structure. Branching enzyme deficiency (Option B, Andersen disease) causes abnormal
glycogen with short branches and cirrhosis. Acid maltase deficiency (Option C, Pompe
disease) causes cardiomegaly and muscle weakness. Muscle phosphorylase deficiency
(Option D, McArdle disease) causes exercise intolerance without hypoglycemia. (NBME:
Biochemistry - Glycogen Storage Diseases)
Question 5
A 30-year-old woman presents with progressive muscle weakness, exercise intolerance,
and myoglobinuria after strenuous exercise. Muscle biopsy shows absence of
phosphorylase activity. Which glycogen storage disease does this represent?
A. von Gierke disease (Type I)
B. Pompe disease (Type II)
C. Cori disease (Type III)
D. McArdle disease (Type V)
Correct Answer: D
D. McArdle disease (Type V) [CORRECT]
Rationale: McArdle disease (Type V) is caused by muscle glycogen phosphorylase
deficiency, presenting with exercise intolerance, muscle cramps, and myoglobinuria due
to inability to break down glycogen for energy. The "second wind" phenomenon may
occur. von Gierke (Option A) affects liver with hypoglycemia. Pompe (Option B) affects
Complete Exam with Answers | USMLE Step 1 Medical
Examination | Pass Guaranteed - A+ Graded
[Section 1: General Principles (Biochemistry, Molecular Biology, Cell
Biology, Genetics) (Q1-35)]
Question 1
A 4-year-old boy is brought to the pediatrician with developmental delay, seizures, and a
musty odor to his urine. His mother reports that he has fair skin and light-colored eyes
compared to family members. Laboratory studies show elevated serum phenylalanine.
Which enzyme deficiency is responsible for this condition?
A. Homogentisate oxidase
B. Phenylalanine hydroxylase
C. Tyrosine kinase
D. Dihydropteridine reductase
Correct Answer: B
B. Phenylalanine hydroxylase [CORRECT]
Rationale: Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase,
which converts phenylalanine to tyrosine. Classic features include intellectual disability,
seizures, fair skin/light hair (due to impaired melanin synthesis from tyrosine
deficiency), and musty/mousy urine odor. Homogentisate oxidase deficiency causes
alkaptonuria (dark urine, ochronosis). Tyrosine kinase is a signaling enzyme unrelated.
,Dihydropteridine reductase deficiency causes a rare variant of hyperphenylalaninemia
but lacks the classic presentation described. (NBME: Biochemistry - Inborn Errors of
Metabolism)
Question 2
A 45-year-old man with chronic alcoholism presents with confusion, ataxia, and
ophthalmoplegia. He is diagnosed with Wernicke encephalopathy. Which vitamin
deficiency is responsible, and what is the biochemical role of this vitamin?
A. Vitamin B12; cofactor for methionine synthase and methylmalonyl-CoA mutase
B. Thiamine (B1); cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase
C. Folate; cofactor for one-carbon transfer reactions in nucleotide synthesis
D. Niacin (B3); component of NAD⁺ and NADP⁺ in redox reactions
Correct Answer: B
B. Thiamine (B1); cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase [CORRECT]
Rationale: Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia) is caused by
thiamine deficiency, common in alcoholism. Thiamine pyrophosphate (TPP) is a
cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase
(pentose phosphate pathway). Vitamin B12 deficiency causes megaloblastic anemia
and subacute combined degeneration. Folate deficiency causes megaloblastic anemia
without neurologic deficits. Niacin deficiency causes pellagra (3 Ds: dermatitis, diarrhea,
dementia). (NBME: Biochemistry - Vitamins)
Question 3
,A researcher is studying a cell line that cannot synthesize purines de novo. The cells are
able to grow when hypoxanthine and thymidine are added to the culture medium. Which
enzyme deficiency is most likely present in these cells?
A. Dihydrofolate reductase
B. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
C. Adenosine deaminase
D. An enzyme in the de novo purine synthesis pathway
Correct Answer: D
D. An enzyme in the de novo purine synthesis pathway [CORRECT]
Rationale: The ability to grow with hypoxanthine (purine salvage) and thymidine
(pyrimidine salvage) indicates the cells can utilize salvage pathways but cannot perform
de novo synthesis. This is the basis of HAT medium selection in hybridoma technology.
HGPRT deficiency (Option B) would prevent hypoxanthine utilization (Lesch-Nyhan
syndrome). Dihydrofolate reductase deficiency affects both pathways. Adenosine
deaminase deficiency causes SCID. (NBME: Molecular Biology - Purine Metabolism)
Question 4
A 2-year-old girl presents with hepatomegaly, fasting hypoglycemia, and lactic acidosis.
A liver biopsy shows glycogen accumulation with normal structure. Which enzyme
deficiency is most likely?
A. Glucose-6-phosphatase
B. Branching enzyme (α-1,6-glucosidase)
C. Acid maltase (α-1,4-glucosidase)
D. Muscle phosphorylase
Correct Answer: A
, A. Glucose-6-phosphatase [CORRECT]
Rationale: Von Gierke disease (Type I glycogen storage disease) is caused by
glucose-6-phosphatase deficiency, presenting with severe fasting hypoglycemia, lactic
acidosis, hyperuricemia, hepatomegaly, and glycogen accumulation with normal
structure. Branching enzyme deficiency (Option B, Andersen disease) causes abnormal
glycogen with short branches and cirrhosis. Acid maltase deficiency (Option C, Pompe
disease) causes cardiomegaly and muscle weakness. Muscle phosphorylase deficiency
(Option D, McArdle disease) causes exercise intolerance without hypoglycemia. (NBME:
Biochemistry - Glycogen Storage Diseases)
Question 5
A 30-year-old woman presents with progressive muscle weakness, exercise intolerance,
and myoglobinuria after strenuous exercise. Muscle biopsy shows absence of
phosphorylase activity. Which glycogen storage disease does this represent?
A. von Gierke disease (Type I)
B. Pompe disease (Type II)
C. Cori disease (Type III)
D. McArdle disease (Type V)
Correct Answer: D
D. McArdle disease (Type V) [CORRECT]
Rationale: McArdle disease (Type V) is caused by muscle glycogen phosphorylase
deficiency, presenting with exercise intolerance, muscle cramps, and myoglobinuria due
to inability to break down glycogen for energy. The "second wind" phenomenon may
occur. von Gierke (Option A) affects liver with hypoglycemia. Pompe (Option B) affects
