NBME CBSE REAL EXAM ACTUAL
EXAM 2026/2027 USMLE Step 1 Medical
Examination | Verified Q&A | Pass
Guaranteed - A+ Graded
[Section 1: General Principles – Biochemistry, Genetics, Cell Biology, Immunology] (35 Questions)
Q1: A 4-year-old boy is brought to the pediatrician with developmental delay, seizures, and a musty
odor to his urine. Laboratory studies reveal elevated phenylalanine levels. His mother is currently
pregnant. Which enzyme deficiency is responsible for this child's condition, and what is the
recommended dietary management for the newborn sibling?
A. Tyrosine hydroxylase; high-protein diet
B. Phenylalanine hydroxylase; phenylalanine-restricted diet [CORRECT]
C. Homogentisate oxidase; low-tyrosine diet
D. Dihydropteridine reductase; tetrahydrobiopterin supplementation
E. Tyrosinase; copper supplementation
Correct Answer: B
Rationale: Phenylketonuria (PKU) results from deficiency of phenylalanine hydroxylase, which converts
phenylalanine to tyrosine. Accumulated phenylalanine causes intellectual disability and the
characteristic musty odor. Newborn screening and lifelong phenylalanine restriction prevent
neurological damage in affected siblings.
Q2: A 28-year-old woman presents with fatigue, pallor, and paresthesias. Laboratory studies show
macrocytic anemia (MCV 110 fL), hypersegmented neutrophils, and elevated methylmalonic acid with
normal homocysteine. Which vitamin deficiency is most likely responsible?
A. Folate
B. Vitamin B12 (cobalamin) [CORRECT]
C. Vitamin B6 (pyridoxine)
,D. Vitamin C
E. Niacin
Correct Answer: B
Rationale: Vitamin B12 deficiency causes macrocytic anemia with elevated methylmalonic acid (due to
impaired conversion of methylmalonyl-CoA to succinyl-CoA) and normal homocysteine if folate levels
are adequate. Folate deficiency elevates homocysteine but not methylmalonic acid.
Q3: A researcher is studying a tumor suppressor gene that regulates the G1/S checkpoint. Mutation of
this gene is associated with Li-Fraumeni syndrome. Which protein does this gene encode?
A. RB1
B. p53 [CORRECT]
C. BRCA1
D. APC
E. PTEN
Correct Answer: B
Rationale: The TP53 gene encodes p53, the "guardian of the genome," which arrests the cell cycle at
G1/S in response to DNA damage. Germline TP53 mutations cause Li-Fraumeni syndrome, characterized
by early-onset multiple cancers including sarcomas, breast cancer, and leukemias.
Q4: A 45-year-old man with chronic alcoholism presents with confusion, ophthalmoplegia, and ataxia.
MRI shows mammillary body atrophy. Which vitamin deficiency is responsible, and what is the
biochemical basis?
A. Vitamin B1 (thiamine); impaired transketolase activity in the pentose phosphate pathway [CORRECT]
B. Vitamin B3 (niacin); impaired NAD+ synthesis
C. Vitamin B6 (pyridoxine); impaired neurotransmitter synthesis
D. Vitamin B12; impaired myelin synthesis
E. Folate; impaired DNA synthesis
Correct Answer: A
Rationale: Wernicke-Korsakoff syndrome results from thiamine (vitamin B1) deficiency, commonly in
alcoholics. Thiamine pyrophosphate is a cofactor for transketolase in the pentose phosphate pathway;
deficiency impairs ribose and NADPH production, leading to lactic acidosis and cellular energy failure.
, Q5: A 2-year-old boy presents with hepatosplenomegaly, failure to thrive, and a cherry-red spot on
macular examination. Enzyme assay reveals deficiency of hexosaminidase A. Which biochemical
pathway is defective?
A. Glycogen metabolism
B. Sphingolipid metabolism [CORRECT]
C. Mucopolysaccharide degradation
D. Purine metabolism
E. Amino acid metabolism
Correct Answer: B
Rationale: Tay-Sachs disease results from hexosaminidase A deficiency, causing accumulation of GM2
ganglioside in lysosomes. This is a sphingolipid storage disorder characterized by cherry-red spot,
neurodegeneration, and death by age 4. It is most common in Ashkenazi Jewish populations.
Q6: A 35-year-old woman with systemic lupus erythematosus is found to have antibodies against
double-stranded DNA. Which type of hypersensitivity reaction is primarily responsible for the renal
damage in this patient?
A. Type I (IgE-mediated)
B. Type II (cytotoxic antibody-mediated)
C. Type III (immune complex-mediated) [CORRECT]
D. Type IV (T-cell-mediated/delayed-type)
E. Type V (stimulatory antibody-mediated)
Correct Answer: C
Rationale: SLE nephritis is a classic Type III hypersensitivity reaction. Anti-dsDNA antibodies form
immune complexes that deposit in the glomerular basement membrane, activating complement and
causing inflammation. This produces the "wire loop" lesions seen on light microscopy.
Q7: A newborn is found to have a deficiency in the enzyme that catalyzes the rate-limiting step of
pyrimidine synthesis. Which enzyme is deficient, and what is the clinical consequence?
A. Dihydroorotate dehydrogenase; orotic aciduria
B. Carbamoyl phosphate synthetase II; orotic aciduria [CORRECT]
C. Aspartate transcarbamoylase; Lesch-Nyhan syndrome
D. Orotidine monophosphate decarboxylase; hereditary orotic aciduria
E. Thymidylate synthase; megaloblastic anemia
Correct Answer: B
Rationale: Carbamoyl phosphate synthetase II (CPS II) catalyzes the committed step of de novo
EXAM 2026/2027 USMLE Step 1 Medical
Examination | Verified Q&A | Pass
Guaranteed - A+ Graded
[Section 1: General Principles – Biochemistry, Genetics, Cell Biology, Immunology] (35 Questions)
Q1: A 4-year-old boy is brought to the pediatrician with developmental delay, seizures, and a musty
odor to his urine. Laboratory studies reveal elevated phenylalanine levels. His mother is currently
pregnant. Which enzyme deficiency is responsible for this child's condition, and what is the
recommended dietary management for the newborn sibling?
A. Tyrosine hydroxylase; high-protein diet
B. Phenylalanine hydroxylase; phenylalanine-restricted diet [CORRECT]
C. Homogentisate oxidase; low-tyrosine diet
D. Dihydropteridine reductase; tetrahydrobiopterin supplementation
E. Tyrosinase; copper supplementation
Correct Answer: B
Rationale: Phenylketonuria (PKU) results from deficiency of phenylalanine hydroxylase, which converts
phenylalanine to tyrosine. Accumulated phenylalanine causes intellectual disability and the
characteristic musty odor. Newborn screening and lifelong phenylalanine restriction prevent
neurological damage in affected siblings.
Q2: A 28-year-old woman presents with fatigue, pallor, and paresthesias. Laboratory studies show
macrocytic anemia (MCV 110 fL), hypersegmented neutrophils, and elevated methylmalonic acid with
normal homocysteine. Which vitamin deficiency is most likely responsible?
A. Folate
B. Vitamin B12 (cobalamin) [CORRECT]
C. Vitamin B6 (pyridoxine)
,D. Vitamin C
E. Niacin
Correct Answer: B
Rationale: Vitamin B12 deficiency causes macrocytic anemia with elevated methylmalonic acid (due to
impaired conversion of methylmalonyl-CoA to succinyl-CoA) and normal homocysteine if folate levels
are adequate. Folate deficiency elevates homocysteine but not methylmalonic acid.
Q3: A researcher is studying a tumor suppressor gene that regulates the G1/S checkpoint. Mutation of
this gene is associated with Li-Fraumeni syndrome. Which protein does this gene encode?
A. RB1
B. p53 [CORRECT]
C. BRCA1
D. APC
E. PTEN
Correct Answer: B
Rationale: The TP53 gene encodes p53, the "guardian of the genome," which arrests the cell cycle at
G1/S in response to DNA damage. Germline TP53 mutations cause Li-Fraumeni syndrome, characterized
by early-onset multiple cancers including sarcomas, breast cancer, and leukemias.
Q4: A 45-year-old man with chronic alcoholism presents with confusion, ophthalmoplegia, and ataxia.
MRI shows mammillary body atrophy. Which vitamin deficiency is responsible, and what is the
biochemical basis?
A. Vitamin B1 (thiamine); impaired transketolase activity in the pentose phosphate pathway [CORRECT]
B. Vitamin B3 (niacin); impaired NAD+ synthesis
C. Vitamin B6 (pyridoxine); impaired neurotransmitter synthesis
D. Vitamin B12; impaired myelin synthesis
E. Folate; impaired DNA synthesis
Correct Answer: A
Rationale: Wernicke-Korsakoff syndrome results from thiamine (vitamin B1) deficiency, commonly in
alcoholics. Thiamine pyrophosphate is a cofactor for transketolase in the pentose phosphate pathway;
deficiency impairs ribose and NADPH production, leading to lactic acidosis and cellular energy failure.
, Q5: A 2-year-old boy presents with hepatosplenomegaly, failure to thrive, and a cherry-red spot on
macular examination. Enzyme assay reveals deficiency of hexosaminidase A. Which biochemical
pathway is defective?
A. Glycogen metabolism
B. Sphingolipid metabolism [CORRECT]
C. Mucopolysaccharide degradation
D. Purine metabolism
E. Amino acid metabolism
Correct Answer: B
Rationale: Tay-Sachs disease results from hexosaminidase A deficiency, causing accumulation of GM2
ganglioside in lysosomes. This is a sphingolipid storage disorder characterized by cherry-red spot,
neurodegeneration, and death by age 4. It is most common in Ashkenazi Jewish populations.
Q6: A 35-year-old woman with systemic lupus erythematosus is found to have antibodies against
double-stranded DNA. Which type of hypersensitivity reaction is primarily responsible for the renal
damage in this patient?
A. Type I (IgE-mediated)
B. Type II (cytotoxic antibody-mediated)
C. Type III (immune complex-mediated) [CORRECT]
D. Type IV (T-cell-mediated/delayed-type)
E. Type V (stimulatory antibody-mediated)
Correct Answer: C
Rationale: SLE nephritis is a classic Type III hypersensitivity reaction. Anti-dsDNA antibodies form
immune complexes that deposit in the glomerular basement membrane, activating complement and
causing inflammation. This produces the "wire loop" lesions seen on light microscopy.
Q7: A newborn is found to have a deficiency in the enzyme that catalyzes the rate-limiting step of
pyrimidine synthesis. Which enzyme is deficient, and what is the clinical consequence?
A. Dihydroorotate dehydrogenase; orotic aciduria
B. Carbamoyl phosphate synthetase II; orotic aciduria [CORRECT]
C. Aspartate transcarbamoylase; Lesch-Nyhan syndrome
D. Orotidine monophosphate decarboxylase; hereditary orotic aciduria
E. Thymidylate synthase; megaloblastic anemia
Correct Answer: B
Rationale: Carbamoyl phosphate synthetase II (CPS II) catalyzes the committed step of de novo
