USMLE STEP 1 2026 – 160 HIGH-YIELD VERIFIED QUESTIONS
WITH VERIFIED ANSWERS & DETAILED EXPLANATIONS 100%
CORRECT ALREADY GRADED A+
1. A 6-month-old infant presents with recurrent infections and failure to thrive.
Lab shows very low B cells and low immunoglobulins of all classes. Which
of the following is the most likely cause?
A. Thymic aplasia
B. Defect in Bruton's tyrosine kinase
C. Defect in RAG1/RAG2
D. Defect in IL-2 receptor γ chain
E. Complement C3 deficiency
Answer: B. Defect in Bruton's tyrosine kinase
Explanation: Bruton's agammaglobulinemia (X-linked) presents in males
with absent B cells and low immunoglobulins; caused by Btk defect.
2. A 55-year-old with hypertension is started on an ACE inhibitor. Which
metabolic change is most likely to occur?
A. Increased bradykinin degradation
B. Decreased angiotensin II levels
C. Increased aldosterone secretion
D. Increased sympathetic tone
E. Increased ACE activity
Answer: B. Decreased angiotensin II levels
Explanation: ACE inhibitors block conversion of Ang I → Ang II, lowering
Ang II and reducing aldosterone; they also increase bradykinin (not
degrade).
,3. A histology slide shows sheets of small blue round cells, with Homer-Wright
rosettes. Which tumor is this most consistent with?
A. Neuroblastoma
B. Rhabdomyosarcoma
C. Wilms tumor
D. Medulloblastoma
E. Ewing sarcoma
Answer: D. Medulloblastoma
Explanation: Small round blue cell tumor in cerebellum with Homer-
Wright rosettes = medulloblastoma (primitive neuroectodermal tumor).
4. Which enzyme deficiency causes classic galactosemia with cataracts,
jaundice soon after feeding, and E. coli sepsis risk in neonates?
A. Galactokinase
B. Galactose-1-phosphate uridyltransferase
C. UDP-galactose 4-epimerase
D. Aldose reductase
E. Fructokinase
Answer: B. Galactose-1-phosphate uridyltransferase
Explanation: Classic galactosemia = GALT deficiency; leads to
accumulation of galactose-1-P, liver dysfunction, and cataracts.
5. A drug that irreversibly inhibits cyclooxygenase (COX) via acetylation and
reduces thromboxane A2 formation is:
A. Ibuprofen
B. Naproxen
C. Aspirin
D. Acetaminophen
E. Celecoxib
Answer: C. Aspirin
, Explanation: Aspirin acetylates COX irreversibly; reduces TXA2 in
platelets causing antiplatelet effect.
6. A patient with vitamin B12 deficiency will have accumulation of which
metabolite?
A. Homocysteine and methylmalonic acid
B. Homocysteine only
C. Succinyl-CoA
D. Lactic acid
E. Propionyl-CoA only
Answer: A. Homocysteine and methylmalonic acid
Explanation: B12 needed for methylmalonyl-CoA mutase →
methylmalonic acid rises; also needed to remethylate homocysteine →
homocysteine rises.
7. Which artery is most likely injured with a midshaft humeral fracture causing
wrist drop?
A. Axillary artery
B. Brachial artery
C. Radial artery
D. Profunda brachii (deep brachial) artery
E. Ulnar artery
Answer: D. Profunda brachii (deep brachial) artery
Explanation: Midshaft humeral fractures often injure the radial nerve and
profunda brachii (radial groove) — radial nerve palsy → wrist drop.
8. A tumor suppressor gene that follows the "two-hit" hypothesis and is
mutated in familial retinoblastoma is:
A. TP53
B. RB1
C. BRCA1
D. PTEN
, E. APC
Answer: B. RB1
Explanation: RB1 is tumor suppressor; familial retinoblastoma occurs when
one germline hit + somatic hit (Knudson two-hit model).
9. A patient has hyperammonemia with hepatic encephalopathy. Which
pathway enzyme would be most relevant to supplement by giving carglumic
acid?
A. Carbamoyl phosphate synthetase I (CPS I) activation via N-
acetylglutamate analog
B. Ornithine transcarbamylase (OTC)
C. Argininosuccinate lyase
D. Arginase
E. Glutamine synthetase
Answer: A. CPS I activation via N-acetylglutamate analog
Explanation: Carglumic acid activates CPS I (mimics N-acetylglutamate) to
enhance urea cycle in hyperammonemia.
10.A bacterium is gram-positive, catalase-negative, and shows α-hemolysis on
blood agar and is bile soluble. This is most likely:
A. Streptococcus pyogenes
B. Streptococcus pneumoniae
C. Enterococcus faecalis
D. Staphylococcus aureus
E. Viridans streptococci
Answer: B. Streptococcus pneumoniae
Explanation: S. pneumoniae is α-hemolytic, optochin sensitive and bile
soluble; catalase negative (a streptococcus).
11.A patient with pheochromocytoma has episodic headaches and hypertension
due to increased:
A. Dopamine only
WITH VERIFIED ANSWERS & DETAILED EXPLANATIONS 100%
CORRECT ALREADY GRADED A+
1. A 6-month-old infant presents with recurrent infections and failure to thrive.
Lab shows very low B cells and low immunoglobulins of all classes. Which
of the following is the most likely cause?
A. Thymic aplasia
B. Defect in Bruton's tyrosine kinase
C. Defect in RAG1/RAG2
D. Defect in IL-2 receptor γ chain
E. Complement C3 deficiency
Answer: B. Defect in Bruton's tyrosine kinase
Explanation: Bruton's agammaglobulinemia (X-linked) presents in males
with absent B cells and low immunoglobulins; caused by Btk defect.
2. A 55-year-old with hypertension is started on an ACE inhibitor. Which
metabolic change is most likely to occur?
A. Increased bradykinin degradation
B. Decreased angiotensin II levels
C. Increased aldosterone secretion
D. Increased sympathetic tone
E. Increased ACE activity
Answer: B. Decreased angiotensin II levels
Explanation: ACE inhibitors block conversion of Ang I → Ang II, lowering
Ang II and reducing aldosterone; they also increase bradykinin (not
degrade).
,3. A histology slide shows sheets of small blue round cells, with Homer-Wright
rosettes. Which tumor is this most consistent with?
A. Neuroblastoma
B. Rhabdomyosarcoma
C. Wilms tumor
D. Medulloblastoma
E. Ewing sarcoma
Answer: D. Medulloblastoma
Explanation: Small round blue cell tumor in cerebellum with Homer-
Wright rosettes = medulloblastoma (primitive neuroectodermal tumor).
4. Which enzyme deficiency causes classic galactosemia with cataracts,
jaundice soon after feeding, and E. coli sepsis risk in neonates?
A. Galactokinase
B. Galactose-1-phosphate uridyltransferase
C. UDP-galactose 4-epimerase
D. Aldose reductase
E. Fructokinase
Answer: B. Galactose-1-phosphate uridyltransferase
Explanation: Classic galactosemia = GALT deficiency; leads to
accumulation of galactose-1-P, liver dysfunction, and cataracts.
5. A drug that irreversibly inhibits cyclooxygenase (COX) via acetylation and
reduces thromboxane A2 formation is:
A. Ibuprofen
B. Naproxen
C. Aspirin
D. Acetaminophen
E. Celecoxib
Answer: C. Aspirin
, Explanation: Aspirin acetylates COX irreversibly; reduces TXA2 in
platelets causing antiplatelet effect.
6. A patient with vitamin B12 deficiency will have accumulation of which
metabolite?
A. Homocysteine and methylmalonic acid
B. Homocysteine only
C. Succinyl-CoA
D. Lactic acid
E. Propionyl-CoA only
Answer: A. Homocysteine and methylmalonic acid
Explanation: B12 needed for methylmalonyl-CoA mutase →
methylmalonic acid rises; also needed to remethylate homocysteine →
homocysteine rises.
7. Which artery is most likely injured with a midshaft humeral fracture causing
wrist drop?
A. Axillary artery
B. Brachial artery
C. Radial artery
D. Profunda brachii (deep brachial) artery
E. Ulnar artery
Answer: D. Profunda brachii (deep brachial) artery
Explanation: Midshaft humeral fractures often injure the radial nerve and
profunda brachii (radial groove) — radial nerve palsy → wrist drop.
8. A tumor suppressor gene that follows the "two-hit" hypothesis and is
mutated in familial retinoblastoma is:
A. TP53
B. RB1
C. BRCA1
D. PTEN
, E. APC
Answer: B. RB1
Explanation: RB1 is tumor suppressor; familial retinoblastoma occurs when
one germline hit + somatic hit (Knudson two-hit model).
9. A patient has hyperammonemia with hepatic encephalopathy. Which
pathway enzyme would be most relevant to supplement by giving carglumic
acid?
A. Carbamoyl phosphate synthetase I (CPS I) activation via N-
acetylglutamate analog
B. Ornithine transcarbamylase (OTC)
C. Argininosuccinate lyase
D. Arginase
E. Glutamine synthetase
Answer: A. CPS I activation via N-acetylglutamate analog
Explanation: Carglumic acid activates CPS I (mimics N-acetylglutamate) to
enhance urea cycle in hyperammonemia.
10.A bacterium is gram-positive, catalase-negative, and shows α-hemolysis on
blood agar and is bile soluble. This is most likely:
A. Streptococcus pyogenes
B. Streptococcus pneumoniae
C. Enterococcus faecalis
D. Staphylococcus aureus
E. Viridans streptococci
Answer: B. Streptococcus pneumoniae
Explanation: S. pneumoniae is α-hemolytic, optochin sensitive and bile
soluble; catalase negative (a streptococcus).
11.A patient with pheochromocytoma has episodic headaches and hypertension
due to increased:
A. Dopamine only
