USMLE STEP 1
HIGH-YIELD
PRACTICE QBANK
2026 Edition
Complete Questions + Detailed Explanations
First Aid & Pathoma Correlated
EXAM SPECIFICATIONS
Question Count: 105 High-Yield Questions
Format: NBME-Style Vignettes
Explanations: Detailed with First Aid 2026 Page Refs
Coverage: All Systems + General Principles
Difficulty: Step 1 Representative
USMLE Step 1 High-Yield Practice Qbank 2026 Page 1
, How to Use This Qbank
QBANK PURPOSE
This is an original, high-yield practice question bank for USMLE Step 1 preparation. Questions are
written to NBME style and difficulty but are NOT actual NBME/USMLE questions. Use for concept
mastery and test-taking practice.
CONTENT DISTRIBUTION
• General Principles (25%) — Biochem, Cell Bio, Genetics, Immuno, Path, Pharm, Micro
• Organ Systems (60%) — Cardio, Pulm, Renal, GI, Endo, Repro, Neuro, MSK, Heme/Onc
• Biostats/Ethics/Behavioral (15%) — Epidemiology, Ethics, Communication, Health Systems
QUESTION FORMAT
Each item is a clinical vignette with 5-7 answer choices. Correct answers are highlighted in green
with checkmark (✓). Every question includes detailed explanation with First Aid 2026 references
and test-taking tips.
STUDY STRATEGY
1. Do questions timed: 90 seconds per question. 2. Read explanation for ALL choices, not just
correct. 3. Annotate First Aid with concepts missed. 4. Review incorrect questions in 1 week. Aim for
70%+ on mixed blocks.
DISCLAIMER
This Qbank contains original questions written for educational purposes. Not affiliated with NBME,
USMLE, or First Aid. Not a substitute for UWorld or NBME practice exams. Use alongside First Aid
2026, Pathoma, Sketchy, and UWorld.
USMLE Step 1 High-Yield Practice Qbank 2026 Page 2
, SECTION I: General Principles - Biochem & Genetics
1. A 2-year-old boy presents with developmental delay, hepatosplenomegaly, and cherry-red
spot on macula. Enzyme deficiency most likely involves:
✓ A. Hexosaminidase A
B. Glucocerebrosidase
C. Sphingomyelinase
D. Alpha-galactosidase A
E. Iduronidase
Rationale: Tay-Sachs disease: Hexosaminidase A deficiency → GM2 ganglioside accumulation. Cherry-red
spot, neurodegeneration, no hepatosplenomegaly (vs Niemann-Pick). Autosomal recessive, Ashkenazi
Jews. FA 2026 p.109. Gaucher: glucocerebrosidase. Niemann-Pick: sphingomyelinase. Fabry:
alpha-galactosidase A.
2. During intense exercise, muscle converts pyruvate to lactate because:
A. Oxygen is abundant
✓ B. NAD+ must be regenerated for glycolysis to continue
C. ATP is not needed
D. Lactate produces more ATP than glucose
E. Mitochondria are inhibited
Rationale: Anaerobic glycolysis: pyruvate → lactate via LDH regenerates NAD+ from NADH, allowing
glycolysis to continue producing 2 ATP/glucose without O2. Lactate not an energy source during production.
FA 2026 p.78.
3. A newborn has ambiguous genitalia, hyponatremia, hyperkalemia, and hypotension. Most
likely enzyme deficiency:
✓ A. 21-hydroxylase
B. 11-beta-hydroxylase
C. 17-alpha-hydroxylase
D. Aromatase
E. 5-alpha-reductase
Rationale: Congenital adrenal hyperplasia, 21-hydroxylase deficiency (90%): ↓cortisol, ↓aldosterone,
↑ACTH, ↑androgens. Virilization in females, salt-wasting crisis. ↑17-OH-progesterone. FA 2026 p.346. 11β:
HTN, not salt-wasting.
4. Von Gierke disease (GSD I) patients develop severe hypoglycemia because:
A. Excess insulin
✓ B. Glucose-6-phosphatase deficiency prevents gluconeogenesis and glycogenolysis
C. GLUT4 defect
D. Glycogen synthase deficiency
E. Pyruvate kinase deficiency
USMLE Step 1 High-Yield Practice Qbank 2026 Page 3
HIGH-YIELD
PRACTICE QBANK
2026 Edition
Complete Questions + Detailed Explanations
First Aid & Pathoma Correlated
EXAM SPECIFICATIONS
Question Count: 105 High-Yield Questions
Format: NBME-Style Vignettes
Explanations: Detailed with First Aid 2026 Page Refs
Coverage: All Systems + General Principles
Difficulty: Step 1 Representative
USMLE Step 1 High-Yield Practice Qbank 2026 Page 1
, How to Use This Qbank
QBANK PURPOSE
This is an original, high-yield practice question bank for USMLE Step 1 preparation. Questions are
written to NBME style and difficulty but are NOT actual NBME/USMLE questions. Use for concept
mastery and test-taking practice.
CONTENT DISTRIBUTION
• General Principles (25%) — Biochem, Cell Bio, Genetics, Immuno, Path, Pharm, Micro
• Organ Systems (60%) — Cardio, Pulm, Renal, GI, Endo, Repro, Neuro, MSK, Heme/Onc
• Biostats/Ethics/Behavioral (15%) — Epidemiology, Ethics, Communication, Health Systems
QUESTION FORMAT
Each item is a clinical vignette with 5-7 answer choices. Correct answers are highlighted in green
with checkmark (✓). Every question includes detailed explanation with First Aid 2026 references
and test-taking tips.
STUDY STRATEGY
1. Do questions timed: 90 seconds per question. 2. Read explanation for ALL choices, not just
correct. 3. Annotate First Aid with concepts missed. 4. Review incorrect questions in 1 week. Aim for
70%+ on mixed blocks.
DISCLAIMER
This Qbank contains original questions written for educational purposes. Not affiliated with NBME,
USMLE, or First Aid. Not a substitute for UWorld or NBME practice exams. Use alongside First Aid
2026, Pathoma, Sketchy, and UWorld.
USMLE Step 1 High-Yield Practice Qbank 2026 Page 2
, SECTION I: General Principles - Biochem & Genetics
1. A 2-year-old boy presents with developmental delay, hepatosplenomegaly, and cherry-red
spot on macula. Enzyme deficiency most likely involves:
✓ A. Hexosaminidase A
B. Glucocerebrosidase
C. Sphingomyelinase
D. Alpha-galactosidase A
E. Iduronidase
Rationale: Tay-Sachs disease: Hexosaminidase A deficiency → GM2 ganglioside accumulation. Cherry-red
spot, neurodegeneration, no hepatosplenomegaly (vs Niemann-Pick). Autosomal recessive, Ashkenazi
Jews. FA 2026 p.109. Gaucher: glucocerebrosidase. Niemann-Pick: sphingomyelinase. Fabry:
alpha-galactosidase A.
2. During intense exercise, muscle converts pyruvate to lactate because:
A. Oxygen is abundant
✓ B. NAD+ must be regenerated for glycolysis to continue
C. ATP is not needed
D. Lactate produces more ATP than glucose
E. Mitochondria are inhibited
Rationale: Anaerobic glycolysis: pyruvate → lactate via LDH regenerates NAD+ from NADH, allowing
glycolysis to continue producing 2 ATP/glucose without O2. Lactate not an energy source during production.
FA 2026 p.78.
3. A newborn has ambiguous genitalia, hyponatremia, hyperkalemia, and hypotension. Most
likely enzyme deficiency:
✓ A. 21-hydroxylase
B. 11-beta-hydroxylase
C. 17-alpha-hydroxylase
D. Aromatase
E. 5-alpha-reductase
Rationale: Congenital adrenal hyperplasia, 21-hydroxylase deficiency (90%): ↓cortisol, ↓aldosterone,
↑ACTH, ↑androgens. Virilization in females, salt-wasting crisis. ↑17-OH-progesterone. FA 2026 p.346. 11β:
HTN, not salt-wasting.
4. Von Gierke disease (GSD I) patients develop severe hypoglycemia because:
A. Excess insulin
✓ B. Glucose-6-phosphatase deficiency prevents gluconeogenesis and glycogenolysis
C. GLUT4 defect
D. Glycogen synthase deficiency
E. Pyruvate kinase deficiency
USMLE Step 1 High-Yield Practice Qbank 2026 Page 3
