NBME CBSE COMPREHENSIVE BASIC SCIENCE EXAM
2026/2027 | USMLE Step 1 Preparation | Complete
QuizBank with Verified Answers | Pass Guaranteed - A+
Graded
Section 1: General Principles - Biochemistry, Molecular Biology,
Genetics, Cell Biology (Q1-30)
Q1. A 4-year-old boy presents with hepatomegaly, fasting hypoglycemia, and lactic
acidosis. A liver biopsy shows glycogen-laden hepatocytes with normal glycogen
structure. Which enzyme deficiency is most likely responsible?
A. Acid alpha-glucosidase (Pompe disease)
B. Glucose-6-phosphatase (von Gierke disease)
C. Debranching enzyme (Cori disease)
D. Branching enzyme (Andersen disease)
Correct Answer: B
Rationale: von Gierke disease (Type I glycogen storage disease) is caused by
glucose-6-phosphatase deficiency, resulting in inability to perform glycogenolysis
and gluconeogenesis, leading to fasting hypoglycemia, lactic acidosis, hyperuricemia,
and hepatomegaly with normal glycogen structure. Option A causes Pompe disease
with cardiomegaly and abnormal lysosomal glycogen. Option C (Cori disease) causes
abnormal glycogen with short outer chains. Option D (Andersen disease) causes
cirrhosis from abnormal glycogen branching. (First Aid 2026, Ch. 3: Glycogen Storage
Diseases)
Q2. A 25-year-old man of Ashkenazi Jewish descent develops progressive neurologic
deterioration starting at age 6 months, with cherry-red spots on funduscopic exam
and no hepatosplenomegaly. Which enzyme deficiency is responsible?
A. Hexosaminidase A
B. Glucocerebrosidase
,C. Sphingomyelinase
D. Galactocerebrosidase
Correct Answer: A
Rationale: Tay-Sachs disease (GM2 gangliosidosis) is caused by hexosaminidase A
deficiency, presenting with progressive neurodegeneration, cherry-red spot (macula
surrounded by retinal whitening from ganglioside accumulation), and normal-sized
liver/spleen. It has increased prevalence in Ashkenazi Jews. Option B causes Gaucher
disease with hepatosplenomegaly. Option C causes Niemann-Pick disease with
hepatosplenomegaly. Option D causes Krabbe disease with peripheral neuropathy.
(First Aid 2026, Ch. 3: Lysosomal Storage Diseases)
Q3. A researcher is studying a tumor suppressor gene that regulates the G1/S
checkpoint by inhibiting cyclin-dependent kinases. Mutations in this gene are found
in many human cancers. Which gene is being studied?
A. RAS
B. MYC
C. RB
D. BCL-2
Correct Answer: C
Rationale: The retinoblastoma (RB) gene product (pRb) binds E2F transcription
factors to prevent cell cycle progression from G1 to S phase. Loss of RB function is
found in retinoblastoma, osteosarcoma, and many other cancers. Option A (RAS) is
an oncogene involved in signal transduction. Option B (MYC) is a transcription factor
oncogene. Option D (BCL-2) inhibits apoptosis. (First Aid 2026, Ch. 3: Cell Cycle
Regulation)
Q4. A 30-year-old woman presents with muscle weakness and myoglobinuria after
intense exercise. A muscle biopsy shows absent myophosphorylase activity. Which
metabolic pathway is defective?
,A. Glycolysis
B. Glycogenolysis
C. Gluconeogenesis
D. Fatty acid oxidation
Correct Answer: B
Rationale: McArdle disease (Type V glycogen storage disease) is caused by
myophosphorylase deficiency, preventing glycogenolysis in muscle. Patients
experience exercise intolerance, muscle cramps, and "second wind" phenomenon
due to impaired muscle glycogen breakdown. Option A would affect all tissues with
different presentation. Option C causes fasting hypoglycemia. Option D causes
hypoketotic hypoglycemia. (First Aid 2026, Ch. 3: Glycogen Storage Diseases)
Q5. A newborn presents with cataracts, hepatomegaly, and mental retardation. Urine
reducing substances are positive, but glucose oxidase test is negative. Which enzyme
deficiency is most likely?
A. Fructokinase
B. Aldolase B
C. Galactose-1-phosphate uridyltransferase
D. Lactase
Correct Answer: C
Rationale: Classic galactosemia is caused by galactose-1-phosphate
uridyltransferase (GALT) deficiency, presenting with cataracts, hepatomegaly,
jaundice, mental retardation, and E. coli sepsis. Positive reducing substances with
negative glucose oxidase indicate non-glucose reducing substances (galactose).
Option A causes benign fructosuria. Option B causes hereditary fructose intolerance.
Option D causes lactose intolerance. (First Aid 2026, Ch. 3: Galactose Metabolism)
Q6. A 45-year-old man with chronic alcoholism presents with painful
ophthalmoplegia, ataxia, and confusion. Which vitamin deficiency is most likely
responsible?
, A. Vitamin B12
B. Thiamine (Vitamin B1)
C. Folate
D. Niacin
Correct Answer: B
Rationale: Wernicke encephalopathy (classic triad: confusion, ophthalmoplegia,
ataxia) is caused by thiamine deficiency, common in alcoholics due to poor nutrition
and impaired absorption. Untreated, it progresses to Korsakoff psychosis (memory
loss, confabulation). Option A causes megaloblastic anemia and subacute combined
degeneration. Option C causes megaloblastic anemia without neurologic deficits.
Option D causes pellagra (3 Ds: dermatitis, diarrhea, dementia). (First Aid 2026, Ch. 5:
Vitamin Deficiencies)
Q7. A patient with homocystinuria is treated with pyridoxine (vitamin B6)
supplementation. Which cofactor does pyridoxine provide for the defective enzyme?
A. Tetrahydrofolate
B. Methylcobalamin
C. Pyridoxal phosphate (PLP)
D. Thiamine pyrophosphate
Correct Answer: C
Rationale: Pyridoxal phosphate (PLP) is the active form of vitamin B6 and serves as
cofactor for cystathionine β-synthase, the enzyme deficient in homocystinuria. Some
patients respond to high-dose B6 supplementation. Option A is folate derivative.
Option B is B12 derivative. Option D is thiamine derivative. (First Aid 2026, Ch. 3:
Amino Acid Metabolism)
Q8. A 2-year-old boy presents with developmental delay, seizures, and fair skin with
light hair. His urine has a musty odor. Which amino acid is elevated in his blood?
2026/2027 | USMLE Step 1 Preparation | Complete
QuizBank with Verified Answers | Pass Guaranteed - A+
Graded
Section 1: General Principles - Biochemistry, Molecular Biology,
Genetics, Cell Biology (Q1-30)
Q1. A 4-year-old boy presents with hepatomegaly, fasting hypoglycemia, and lactic
acidosis. A liver biopsy shows glycogen-laden hepatocytes with normal glycogen
structure. Which enzyme deficiency is most likely responsible?
A. Acid alpha-glucosidase (Pompe disease)
B. Glucose-6-phosphatase (von Gierke disease)
C. Debranching enzyme (Cori disease)
D. Branching enzyme (Andersen disease)
Correct Answer: B
Rationale: von Gierke disease (Type I glycogen storage disease) is caused by
glucose-6-phosphatase deficiency, resulting in inability to perform glycogenolysis
and gluconeogenesis, leading to fasting hypoglycemia, lactic acidosis, hyperuricemia,
and hepatomegaly with normal glycogen structure. Option A causes Pompe disease
with cardiomegaly and abnormal lysosomal glycogen. Option C (Cori disease) causes
abnormal glycogen with short outer chains. Option D (Andersen disease) causes
cirrhosis from abnormal glycogen branching. (First Aid 2026, Ch. 3: Glycogen Storage
Diseases)
Q2. A 25-year-old man of Ashkenazi Jewish descent develops progressive neurologic
deterioration starting at age 6 months, with cherry-red spots on funduscopic exam
and no hepatosplenomegaly. Which enzyme deficiency is responsible?
A. Hexosaminidase A
B. Glucocerebrosidase
,C. Sphingomyelinase
D. Galactocerebrosidase
Correct Answer: A
Rationale: Tay-Sachs disease (GM2 gangliosidosis) is caused by hexosaminidase A
deficiency, presenting with progressive neurodegeneration, cherry-red spot (macula
surrounded by retinal whitening from ganglioside accumulation), and normal-sized
liver/spleen. It has increased prevalence in Ashkenazi Jews. Option B causes Gaucher
disease with hepatosplenomegaly. Option C causes Niemann-Pick disease with
hepatosplenomegaly. Option D causes Krabbe disease with peripheral neuropathy.
(First Aid 2026, Ch. 3: Lysosomal Storage Diseases)
Q3. A researcher is studying a tumor suppressor gene that regulates the G1/S
checkpoint by inhibiting cyclin-dependent kinases. Mutations in this gene are found
in many human cancers. Which gene is being studied?
A. RAS
B. MYC
C. RB
D. BCL-2
Correct Answer: C
Rationale: The retinoblastoma (RB) gene product (pRb) binds E2F transcription
factors to prevent cell cycle progression from G1 to S phase. Loss of RB function is
found in retinoblastoma, osteosarcoma, and many other cancers. Option A (RAS) is
an oncogene involved in signal transduction. Option B (MYC) is a transcription factor
oncogene. Option D (BCL-2) inhibits apoptosis. (First Aid 2026, Ch. 3: Cell Cycle
Regulation)
Q4. A 30-year-old woman presents with muscle weakness and myoglobinuria after
intense exercise. A muscle biopsy shows absent myophosphorylase activity. Which
metabolic pathway is defective?
,A. Glycolysis
B. Glycogenolysis
C. Gluconeogenesis
D. Fatty acid oxidation
Correct Answer: B
Rationale: McArdle disease (Type V glycogen storage disease) is caused by
myophosphorylase deficiency, preventing glycogenolysis in muscle. Patients
experience exercise intolerance, muscle cramps, and "second wind" phenomenon
due to impaired muscle glycogen breakdown. Option A would affect all tissues with
different presentation. Option C causes fasting hypoglycemia. Option D causes
hypoketotic hypoglycemia. (First Aid 2026, Ch. 3: Glycogen Storage Diseases)
Q5. A newborn presents with cataracts, hepatomegaly, and mental retardation. Urine
reducing substances are positive, but glucose oxidase test is negative. Which enzyme
deficiency is most likely?
A. Fructokinase
B. Aldolase B
C. Galactose-1-phosphate uridyltransferase
D. Lactase
Correct Answer: C
Rationale: Classic galactosemia is caused by galactose-1-phosphate
uridyltransferase (GALT) deficiency, presenting with cataracts, hepatomegaly,
jaundice, mental retardation, and E. coli sepsis. Positive reducing substances with
negative glucose oxidase indicate non-glucose reducing substances (galactose).
Option A causes benign fructosuria. Option B causes hereditary fructose intolerance.
Option D causes lactose intolerance. (First Aid 2026, Ch. 3: Galactose Metabolism)
Q6. A 45-year-old man with chronic alcoholism presents with painful
ophthalmoplegia, ataxia, and confusion. Which vitamin deficiency is most likely
responsible?
, A. Vitamin B12
B. Thiamine (Vitamin B1)
C. Folate
D. Niacin
Correct Answer: B
Rationale: Wernicke encephalopathy (classic triad: confusion, ophthalmoplegia,
ataxia) is caused by thiamine deficiency, common in alcoholics due to poor nutrition
and impaired absorption. Untreated, it progresses to Korsakoff psychosis (memory
loss, confabulation). Option A causes megaloblastic anemia and subacute combined
degeneration. Option C causes megaloblastic anemia without neurologic deficits.
Option D causes pellagra (3 Ds: dermatitis, diarrhea, dementia). (First Aid 2026, Ch. 5:
Vitamin Deficiencies)
Q7. A patient with homocystinuria is treated with pyridoxine (vitamin B6)
supplementation. Which cofactor does pyridoxine provide for the defective enzyme?
A. Tetrahydrofolate
B. Methylcobalamin
C. Pyridoxal phosphate (PLP)
D. Thiamine pyrophosphate
Correct Answer: C
Rationale: Pyridoxal phosphate (PLP) is the active form of vitamin B6 and serves as
cofactor for cystathionine β-synthase, the enzyme deficient in homocystinuria. Some
patients respond to high-dose B6 supplementation. Option A is folate derivative.
Option B is B12 derivative. Option D is thiamine derivative. (First Aid 2026, Ch. 3:
Amino Acid Metabolism)
Q8. A 2-year-old boy presents with developmental delay, seizures, and fair skin with
light hair. His urine has a musty odor. Which amino acid is elevated in his blood?
