NBME CBSE REAL EXAM 200 QUESTIONS 2026/2027
Complete Exam with Answers | USMLE Step 1 Medical
Examination | Pass Guaranteed - A+ Graded
Question 1
A 4-year-old boy is brought to the pediatrician with developmental delay, seizures, and
a musty odor to his urine. His mother reports that he has fair skin and light-colored eyes
compared to family members. Laboratory studies show elevated serum phenylalanine.
Which enzyme deficiency is responsible for this condition?
A. Homogentisate oxidase
B. Phenylalanine hydroxylase
C. Tyrosine kinase
D. Dihydropteridine reductase
Correct Answer: B
B. Phenylalanine hydroxylase [CORRECT]
Rationale: Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase,
which converts phenylalanine to tyrosine. Classic features include intellectual disability,
seizures, fair skin/light hair, and musty urine odor. (NBME: Biochemistry - Inborn Errors
of Metabolism)
Question 2
A 45-year-old man with chronic alcoholism presents with confusion, ataxia, and
ophthalmoplegia. He is diagnosed with Wernicke encephalopathy. Which vitamin
deficiency is responsible, and what is the biochemical role of this vitamin?
A. Vitamin B12; cofactor for methionine synthase and methylmalonyl-CoA mutase
B. Thiamine (B1); cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase
C. Folate; cofactor for one-carbon transfer reactions in nucleotide synthesis
D. Niacin (B3); component of NAD+ and NADP+ in redox reactions
Correct Answer: B
B. Thiamine (B1); cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase [CORRECT]
Rationale: Wernicke encephalopathy is caused by thiamine deficiency. Thiamine
,pyrophosphate (TPP) is a cofactor for the listed enzymes. (NBME: Biochemistry -
Vitamins)
Question 3
A researcher is studying a cell line that cannot synthesize purines de novo. The cells are
able to grow when hypoxanthine and thymidine are added to the culture medium.
Which enzyme deficiency is most likely present in these cells?
A. Dihydrofolate reductase
B. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
C. Adenosine deaminase
D. An enzyme in the de novo purine synthesis pathway
Correct Answer: D
D. An enzyme in the de novo purine synthesis pathway [CORRECT]
Rationale: Growth with hypoxanthine and thymidine indicates salvage pathway
utilization but inability to synthesize purines de novo, suggesting a defect in de novo
synthesis. (NBME: Molecular Biology - Purine Metabolism)
Question 4
A 2-year-old girl presents with hepatomegaly, fasting hypoglycemia, and lactic acidosis.
A liver biopsy shows glycogen accumulation with normal structure. Which enzyme
deficiency is most likely?
A. Glucose-6-phosphatase
B. Branching enzyme (α-1,6-glucosidase)
C. Acid maltase (α-1,4-glucosidase)
D. Muscle phosphorylase
Correct Answer: A
A. Glucose-6-phosphatase [CORRECT]
Rationale: Von Gierke disease (Type I glycogen storage disease) is caused by glucose-6-
phosphatase deficiency, presenting with severe fasting hypoglycemia, lactic acidosis,
hepatomegaly, and normal glycogen structure. (NBME: Biochemistry - Glycogen Storage
Diseases)
Question 5
A 30-year-old woman presents with progressive muscle weakness, exercise intolerance,
and myoglobinuria after strenuous exercise. Muscle biopsy shows absence of
phosphorylase activity. Which glycogen storage disease does this represent?
A. von Gierke disease (Type I)
B. Pompe disease (Type II)
C. Cori disease (Type III)
D. McArdle disease (Type V)
Correct Answer: D
,D. McArdle disease (Type V) [CORRECT]
Rationale: McArdle disease is caused by muscle glycogen phosphorylase deficiency,
presenting with exercise intolerance, muscle cramps, and myoglobinuria. (NBME:
Biochemistry - Glycogen Storage Diseases)
Question 6
A newborn is found to have cataracts, hepatomegaly, and jaundice. Urine reducing
substances are positive, but glucose oxidase test is negative. Which enzyme deficiency is
most likely?
A. Galactokinase
B. UDP-galactose-4-epimerase
C. Galactose-1-phosphate uridyltransferase (GALT)
D. Fructokinase
Correct Answer: C
C. Galactose-1-phosphate uridyltransferase (GALT) [CORRECT]
Rationale: Classic galactosemia is caused by GALT deficiency, presenting with cataracts,
hepatomegaly, jaundice, and E. coli sepsis. Urine reducing substances positive but
glucose oxidase negative indicates galactose. (NBME: Biochemistry - Carbohydrate
Metabolism)
Question 7
A 55-year-old man with a history of alcohol abuse presents with painful fat deposits on
his elbows and knees. Biopsy shows cholesterol clefts within lipid-laden macrophages.
Which lipoprotein is most likely elevated?
A. Chylomicrons
B. VLDL
C. LDL
D. HDL
Correct Answer: B
B. VLDL [CORRECT]
Rationale: Chronic alcohol abuse can lead to hyperlipoproteinemia, specifically elevated
VLDL (due to increased fatty acid synthesis and VLDL secretion). Eruptive xanthomas
(painful fat deposits with cholesterol clefts in macrophages) are associated with
hypertriglyceridemia, often from VLDL elevation. (NBME: Biochemistry - Lipid
Metabolism)
Question 8
A 6-month-old infant presents with progressive hypotonia, cardiomegaly, and
macroglossia. A muscle biopsy shows glycogen accumulation within lysosomes. Which
enzyme deficiency is most likely?
A. Glucose-6-phosphatase
, B. Acid maltase
C. Muscle phosphorylase
D. Debranching enzyme
Correct Answer: B
B. Acid maltase [CORRECT]
Rationale: Pompe disease (Type II glycogen storage disease) is caused by acid alpha-
glucosidase (acid maltase) deficiency, leading to lysosomal glycogen accumulation,
cardiomegaly, macroglossia, and hypotonia. (NBME: Biochemistry - Glycogen Storage
Diseases)
Question 9
A 20-year-old man presents with painless reddish-brown discoloration of his sclera and
ear cartilage. His urine turns black when left standing. Which enzyme is deficient?
A. Phenylalanine hydroxylase
B. Homogentisate 1,2-dioxygenase
C. Tyrosinase
D. Fumarylacetoacetate hydrolase
Correct Answer: B
B. Homogentisate 1,2-dioxygenase [CORRECT]
Rationale: Alkaptonuria (ochronosis) is due to homogentisate 1,2-dioxygenase
deficiency. Homogentisic acid accumulates and oxidizes to a black pigment in urine and
connective tissues. (NBME: Biochemistry - Inborn Errors of Metabolism)
Question 10
A 3-year-old boy presents with self-mutilation of his lips and fingers, gouty arthritis, and
developmental delay. Serum uric acid is markedly elevated. Which enzyme is deficient?
A. Adenosine deaminase
B. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
C. Purine nucleoside phosphorylase
D. Xanthine oxidase
Correct Answer: B
B. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) [CORRECT]
Rationale: Lesch-Nyhan syndrome is caused by HGPRT deficiency, leading to
overproduction of uric acid and self-injurious behavior. (NBME: Biochemistry - Purine
Metabolism)
Question 11
A 35-year-old woman presents with intermittent abdominal pain, neuropsychiatric
symptoms, and reddish urine that darkens upon exposure to light. She has a history of
photosensitivity. Which enzyme deficiency is most likely?
A. Porphobilinogen deaminase
Complete Exam with Answers | USMLE Step 1 Medical
Examination | Pass Guaranteed - A+ Graded
Question 1
A 4-year-old boy is brought to the pediatrician with developmental delay, seizures, and
a musty odor to his urine. His mother reports that he has fair skin and light-colored eyes
compared to family members. Laboratory studies show elevated serum phenylalanine.
Which enzyme deficiency is responsible for this condition?
A. Homogentisate oxidase
B. Phenylalanine hydroxylase
C. Tyrosine kinase
D. Dihydropteridine reductase
Correct Answer: B
B. Phenylalanine hydroxylase [CORRECT]
Rationale: Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase,
which converts phenylalanine to tyrosine. Classic features include intellectual disability,
seizures, fair skin/light hair, and musty urine odor. (NBME: Biochemistry - Inborn Errors
of Metabolism)
Question 2
A 45-year-old man with chronic alcoholism presents with confusion, ataxia, and
ophthalmoplegia. He is diagnosed with Wernicke encephalopathy. Which vitamin
deficiency is responsible, and what is the biochemical role of this vitamin?
A. Vitamin B12; cofactor for methionine synthase and methylmalonyl-CoA mutase
B. Thiamine (B1); cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase
C. Folate; cofactor for one-carbon transfer reactions in nucleotide synthesis
D. Niacin (B3); component of NAD+ and NADP+ in redox reactions
Correct Answer: B
B. Thiamine (B1); cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase [CORRECT]
Rationale: Wernicke encephalopathy is caused by thiamine deficiency. Thiamine
,pyrophosphate (TPP) is a cofactor for the listed enzymes. (NBME: Biochemistry -
Vitamins)
Question 3
A researcher is studying a cell line that cannot synthesize purines de novo. The cells are
able to grow when hypoxanthine and thymidine are added to the culture medium.
Which enzyme deficiency is most likely present in these cells?
A. Dihydrofolate reductase
B. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
C. Adenosine deaminase
D. An enzyme in the de novo purine synthesis pathway
Correct Answer: D
D. An enzyme in the de novo purine synthesis pathway [CORRECT]
Rationale: Growth with hypoxanthine and thymidine indicates salvage pathway
utilization but inability to synthesize purines de novo, suggesting a defect in de novo
synthesis. (NBME: Molecular Biology - Purine Metabolism)
Question 4
A 2-year-old girl presents with hepatomegaly, fasting hypoglycemia, and lactic acidosis.
A liver biopsy shows glycogen accumulation with normal structure. Which enzyme
deficiency is most likely?
A. Glucose-6-phosphatase
B. Branching enzyme (α-1,6-glucosidase)
C. Acid maltase (α-1,4-glucosidase)
D. Muscle phosphorylase
Correct Answer: A
A. Glucose-6-phosphatase [CORRECT]
Rationale: Von Gierke disease (Type I glycogen storage disease) is caused by glucose-6-
phosphatase deficiency, presenting with severe fasting hypoglycemia, lactic acidosis,
hepatomegaly, and normal glycogen structure. (NBME: Biochemistry - Glycogen Storage
Diseases)
Question 5
A 30-year-old woman presents with progressive muscle weakness, exercise intolerance,
and myoglobinuria after strenuous exercise. Muscle biopsy shows absence of
phosphorylase activity. Which glycogen storage disease does this represent?
A. von Gierke disease (Type I)
B. Pompe disease (Type II)
C. Cori disease (Type III)
D. McArdle disease (Type V)
Correct Answer: D
,D. McArdle disease (Type V) [CORRECT]
Rationale: McArdle disease is caused by muscle glycogen phosphorylase deficiency,
presenting with exercise intolerance, muscle cramps, and myoglobinuria. (NBME:
Biochemistry - Glycogen Storage Diseases)
Question 6
A newborn is found to have cataracts, hepatomegaly, and jaundice. Urine reducing
substances are positive, but glucose oxidase test is negative. Which enzyme deficiency is
most likely?
A. Galactokinase
B. UDP-galactose-4-epimerase
C. Galactose-1-phosphate uridyltransferase (GALT)
D. Fructokinase
Correct Answer: C
C. Galactose-1-phosphate uridyltransferase (GALT) [CORRECT]
Rationale: Classic galactosemia is caused by GALT deficiency, presenting with cataracts,
hepatomegaly, jaundice, and E. coli sepsis. Urine reducing substances positive but
glucose oxidase negative indicates galactose. (NBME: Biochemistry - Carbohydrate
Metabolism)
Question 7
A 55-year-old man with a history of alcohol abuse presents with painful fat deposits on
his elbows and knees. Biopsy shows cholesterol clefts within lipid-laden macrophages.
Which lipoprotein is most likely elevated?
A. Chylomicrons
B. VLDL
C. LDL
D. HDL
Correct Answer: B
B. VLDL [CORRECT]
Rationale: Chronic alcohol abuse can lead to hyperlipoproteinemia, specifically elevated
VLDL (due to increased fatty acid synthesis and VLDL secretion). Eruptive xanthomas
(painful fat deposits with cholesterol clefts in macrophages) are associated with
hypertriglyceridemia, often from VLDL elevation. (NBME: Biochemistry - Lipid
Metabolism)
Question 8
A 6-month-old infant presents with progressive hypotonia, cardiomegaly, and
macroglossia. A muscle biopsy shows glycogen accumulation within lysosomes. Which
enzyme deficiency is most likely?
A. Glucose-6-phosphatase
, B. Acid maltase
C. Muscle phosphorylase
D. Debranching enzyme
Correct Answer: B
B. Acid maltase [CORRECT]
Rationale: Pompe disease (Type II glycogen storage disease) is caused by acid alpha-
glucosidase (acid maltase) deficiency, leading to lysosomal glycogen accumulation,
cardiomegaly, macroglossia, and hypotonia. (NBME: Biochemistry - Glycogen Storage
Diseases)
Question 9
A 20-year-old man presents with painless reddish-brown discoloration of his sclera and
ear cartilage. His urine turns black when left standing. Which enzyme is deficient?
A. Phenylalanine hydroxylase
B. Homogentisate 1,2-dioxygenase
C. Tyrosinase
D. Fumarylacetoacetate hydrolase
Correct Answer: B
B. Homogentisate 1,2-dioxygenase [CORRECT]
Rationale: Alkaptonuria (ochronosis) is due to homogentisate 1,2-dioxygenase
deficiency. Homogentisic acid accumulates and oxidizes to a black pigment in urine and
connective tissues. (NBME: Biochemistry - Inborn Errors of Metabolism)
Question 10
A 3-year-old boy presents with self-mutilation of his lips and fingers, gouty arthritis, and
developmental delay. Serum uric acid is markedly elevated. Which enzyme is deficient?
A. Adenosine deaminase
B. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
C. Purine nucleoside phosphorylase
D. Xanthine oxidase
Correct Answer: B
B. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) [CORRECT]
Rationale: Lesch-Nyhan syndrome is caused by HGPRT deficiency, leading to
overproduction of uric acid and self-injurious behavior. (NBME: Biochemistry - Purine
Metabolism)
Question 11
A 35-year-old woman presents with intermittent abdominal pain, neuropsychiatric
symptoms, and reddish urine that darkens upon exposure to light. She has a history of
photosensitivity. Which enzyme deficiency is most likely?
A. Porphobilinogen deaminase
