2026/2027
NBME CBSE (USMLE Step 1
Medical Exam) Complete Self-
Assessment, Practice Quiz, and
Board Review Manual 2026/2027
Edition
Question 1: Alkaptonuria biochemical defect
Alkaptonuria is an autosomal recessive disorder caused by deficiency of an enzyme
involved in tyrosine metabolism. Which enzyme is most likely deficient?
A. Tyrosine hydroxylase
B. Phenylalanine hydroxylase
C. Homogentisate oxidase
D. Dopamine β-hydroxylase
Correct Answer: C. Homogentisate oxidase
Rationale:
Alkaptonuria results from deficiency of homogentisate oxidase, leading to
accumulation of homogentisic acid. This causes dark urine, ochronosis, and
connective tissue pigmentation. Other enzymes listed are involved in catecholamine
or phenylalanine metabolism and are not responsible for this condition.
Question 2: Erectile dysfunction cause
differentiation
A 68-year-old man reports inability to maintain erection with a new partner but
normal masturbation and nocturnal erections. Libido is normal. What is the most
likely pattern?
A. Decreased nocturnal erections, decreased libido
B. Decreased nocturnal erections, normal libido
C. Normal nocturnal erections, decreased libido
D. Normal nocturnal erections, normal libido
Correct Answer: D. Normal nocturnal erections, normal libido
Rationale:
Normal nocturnal and masturbation erections indicate intact vascular and neurologic
,2026/2027
function, suggesting psychogenic erectile dysfunction. Libido remains normal because
hormonal and psychological baseline drive is intact. Organic causes (vascular,
neurologic, endocrine) would typically reduce nocturnal erections.
Question 3: Excitotoxicity after stroke
Following cerebral ischemia, neuronal death is primarily mediated by excessive
release of which neurotransmitter?
A. Acetylcholine
B. GABA
C. Glutamate
D. Glycine
Correct Answer: C. Glutamate
Rationale:
Glutamate excitotoxicity occurs after ischemia due to excessive activation of NMDA
receptors, causing calcium influx and neuronal apoptosis. This leads to enzyme
activation, oxidative stress, and cell death. Other neurotransmitters do not mediate this
excitotoxic cascade.
Question 4: Pediatric rickets presentation
A child presents with bowing of legs, frontal bossing, and delayed tooth eruption.
What is the most likely cause?
A. Vitamin A deficiency
B. Vitamin D deficiency
C. Vitamin C deficiency
D. Vitamin K deficiency
Correct Answer: B. Vitamin D deficiency
Rationale:
Vitamin D deficiency causes rickets, characterized by defective bone mineralization
leading to skeletal deformities such as bowed legs, delayed closure of growth plates,
and dental abnormalities. Other vitamin deficiencies cause bleeding, scurvy, or vision
issues but not bone deformities.
Question 5: Alcohol and acetaminophen
toxicity
A chronic alcoholic develops acute liver failure after acetaminophen overdose. What
enzyme is responsible for increased toxicity?
,2026/2027
A. Alcohol dehydrogenase
B. UDP-glucuronosyltransferase
C. Sulfotransferase
D. Cytochrome P450 2E1
Correct Answer: D. Cytochrome P450 2E1
Rationale:
Chronic alcohol use induces CYP2E1, increasing conversion of acetaminophen into
toxic NAPQI. This depletes glutathione and causes hepatotoxicity. Phase II pathways
(glucuronidation, sulfation) are protective and become saturated in overdose.
Question 6: Best marker of oxidative stress
Which laboratory marker best reflects hepatic oxidative stress?
A. CRP mRNA
B. Nitrated proteins
C. Cytochrome P450 levels
D. GSH:GSSG ratio
Correct Answer: D. GSH:GSSG ratio
Rationale:
The GSH:GSSG ratio directly measures intracellular redox balance. A reduced ratio
indicates oxidative stress. Other markers are indirect or reflect inflammation rather
than oxidative status.
Question 7: Granuloma formation mechanism
A patient has noncaseating granulomas. What immune mechanism is responsible?
A. Type I hypersensitivity
B. Type II hypersensitivity
C. Type III hypersensitivity
D. Type IV hypersensitivity
Correct Answer: D. Type IV hypersensitivity
Rationale:
Granuloma formation is mediated by T-cell–driven delayed hypersensitivity (Type
IV). Activated macrophages and Th1 cells form granulomas in diseases like
sarcoidosis. Antibody-mediated hypersensitivities do not form granulomas.
Question 8: Embryology timing
, 2026/2027
At ~20 days gestation, which structure is present?
A. Fully formed neural tube
B. Two germ layers
C. Neural plate present
D. Mature placenta
Correct Answer: C. Neural plate present
Rationale:
During week 3, gastrulation has formed three germ layers and the neural plate is
developing but not yet closed into a neural tube. Placenta is not mature, and somites
are beginning to form.
Question 9: Aging lung changes
Which change is expected in a healthy elderly adult?
A. Decreased residual volume
B. Increased arterial PO₂
C. Increased A-a gradient
D. Decreased lung compliance
Correct Answer: C. Increased A-a gradient
Rationale:
Aging causes loss of alveolar surface area and ventilation-perfusion mismatch,
increasing the A-a gradient. Residual volume increases, arterial oxygen decreases, and
chest wall compliance decreases.
Question 10: Statistical test for allele
comparison
A study compares allele frequencies between two groups. What test is appropriate?
A. ANOVA
B. Chi-square test
C. t-test
D. Linear regression
Correct Answer: B. Chi-square test
Rationale:
Chi-square test compares categorical variables such as allele presence between groups.
t-tests and ANOVA compare means, not proportions.
NBME CBSE (USMLE Step 1
Medical Exam) Complete Self-
Assessment, Practice Quiz, and
Board Review Manual 2026/2027
Edition
Question 1: Alkaptonuria biochemical defect
Alkaptonuria is an autosomal recessive disorder caused by deficiency of an enzyme
involved in tyrosine metabolism. Which enzyme is most likely deficient?
A. Tyrosine hydroxylase
B. Phenylalanine hydroxylase
C. Homogentisate oxidase
D. Dopamine β-hydroxylase
Correct Answer: C. Homogentisate oxidase
Rationale:
Alkaptonuria results from deficiency of homogentisate oxidase, leading to
accumulation of homogentisic acid. This causes dark urine, ochronosis, and
connective tissue pigmentation. Other enzymes listed are involved in catecholamine
or phenylalanine metabolism and are not responsible for this condition.
Question 2: Erectile dysfunction cause
differentiation
A 68-year-old man reports inability to maintain erection with a new partner but
normal masturbation and nocturnal erections. Libido is normal. What is the most
likely pattern?
A. Decreased nocturnal erections, decreased libido
B. Decreased nocturnal erections, normal libido
C. Normal nocturnal erections, decreased libido
D. Normal nocturnal erections, normal libido
Correct Answer: D. Normal nocturnal erections, normal libido
Rationale:
Normal nocturnal and masturbation erections indicate intact vascular and neurologic
,2026/2027
function, suggesting psychogenic erectile dysfunction. Libido remains normal because
hormonal and psychological baseline drive is intact. Organic causes (vascular,
neurologic, endocrine) would typically reduce nocturnal erections.
Question 3: Excitotoxicity after stroke
Following cerebral ischemia, neuronal death is primarily mediated by excessive
release of which neurotransmitter?
A. Acetylcholine
B. GABA
C. Glutamate
D. Glycine
Correct Answer: C. Glutamate
Rationale:
Glutamate excitotoxicity occurs after ischemia due to excessive activation of NMDA
receptors, causing calcium influx and neuronal apoptosis. This leads to enzyme
activation, oxidative stress, and cell death. Other neurotransmitters do not mediate this
excitotoxic cascade.
Question 4: Pediatric rickets presentation
A child presents with bowing of legs, frontal bossing, and delayed tooth eruption.
What is the most likely cause?
A. Vitamin A deficiency
B. Vitamin D deficiency
C. Vitamin C deficiency
D. Vitamin K deficiency
Correct Answer: B. Vitamin D deficiency
Rationale:
Vitamin D deficiency causes rickets, characterized by defective bone mineralization
leading to skeletal deformities such as bowed legs, delayed closure of growth plates,
and dental abnormalities. Other vitamin deficiencies cause bleeding, scurvy, or vision
issues but not bone deformities.
Question 5: Alcohol and acetaminophen
toxicity
A chronic alcoholic develops acute liver failure after acetaminophen overdose. What
enzyme is responsible for increased toxicity?
,2026/2027
A. Alcohol dehydrogenase
B. UDP-glucuronosyltransferase
C. Sulfotransferase
D. Cytochrome P450 2E1
Correct Answer: D. Cytochrome P450 2E1
Rationale:
Chronic alcohol use induces CYP2E1, increasing conversion of acetaminophen into
toxic NAPQI. This depletes glutathione and causes hepatotoxicity. Phase II pathways
(glucuronidation, sulfation) are protective and become saturated in overdose.
Question 6: Best marker of oxidative stress
Which laboratory marker best reflects hepatic oxidative stress?
A. CRP mRNA
B. Nitrated proteins
C. Cytochrome P450 levels
D. GSH:GSSG ratio
Correct Answer: D. GSH:GSSG ratio
Rationale:
The GSH:GSSG ratio directly measures intracellular redox balance. A reduced ratio
indicates oxidative stress. Other markers are indirect or reflect inflammation rather
than oxidative status.
Question 7: Granuloma formation mechanism
A patient has noncaseating granulomas. What immune mechanism is responsible?
A. Type I hypersensitivity
B. Type II hypersensitivity
C. Type III hypersensitivity
D. Type IV hypersensitivity
Correct Answer: D. Type IV hypersensitivity
Rationale:
Granuloma formation is mediated by T-cell–driven delayed hypersensitivity (Type
IV). Activated macrophages and Th1 cells form granulomas in diseases like
sarcoidosis. Antibody-mediated hypersensitivities do not form granulomas.
Question 8: Embryology timing
, 2026/2027
At ~20 days gestation, which structure is present?
A. Fully formed neural tube
B. Two germ layers
C. Neural plate present
D. Mature placenta
Correct Answer: C. Neural plate present
Rationale:
During week 3, gastrulation has formed three germ layers and the neural plate is
developing but not yet closed into a neural tube. Placenta is not mature, and somites
are beginning to form.
Question 9: Aging lung changes
Which change is expected in a healthy elderly adult?
A. Decreased residual volume
B. Increased arterial PO₂
C. Increased A-a gradient
D. Decreased lung compliance
Correct Answer: C. Increased A-a gradient
Rationale:
Aging causes loss of alveolar surface area and ventilation-perfusion mismatch,
increasing the A-a gradient. Residual volume increases, arterial oxygen decreases, and
chest wall compliance decreases.
Question 10: Statistical test for allele
comparison
A study compares allele frequencies between two groups. What test is appropriate?
A. ANOVA
B. Chi-square test
C. t-test
D. Linear regression
Correct Answer: B. Chi-square test
Rationale:
Chi-square test compares categorical variables such as allele presence between groups.
t-tests and ANOVA compare means, not proportions.
