USMLE Step 1| QUESTION AND ANSWERS |REVISED AND
VERIFIED QUSTION| GRADED A+|LATEST UPDATE 2026
Biochemistry & Genetics
1.
A 6-month-old boy is brought to the physician because of recurrent vomiting, lethargy, and
seizures after introduction of fruit juice into his diet. Laboratory studies show hypoglycemia and
elevated liver enzymes. Urine testing reveals reducing substances. Which enzyme deficiency is
most likely responsible?
A. Glucose-6-phosphatase
B. Fructokinase
C. Aldolase B
D. Galactose-1-phosphate uridyltransferase
E. Pyruvate carboxylase
Answer: C. Aldolase B
Rationale: Hereditary fructose intolerance is caused by aldolase B deficiency. Fructose-1-
phosphate accumulates after ingestion of fructose or sucrose, trapping phosphate and impairing
gluconeogenesis, leading to severe hypoglycemia.
2.
A newborn develops jaundice, hepatomegaly, vomiting, and failure to thrive after breastfeeding.
Laboratory studies show increased conjugated bilirubin and cataracts. Which enzyme is
deficient?
A. Galactokinase
B. Aldolase B
C. Galactose-1-phosphate uridyltransferase
D. UDP-glucose dehydrogenase
E. Glucose-6-phosphatase
Answer: C. Galactose-1-phosphate uridyltransferase
Rationale: Classic galactosemia results from GALT deficiency. Galactose-1-phosphate
accumulates and can cause liver dysfunction, jaundice, E. coli sepsis, and cataracts.
,3.
A patient with chronic alcoholism develops confusion, ophthalmoplegia, and ataxia. Which
enzyme is most likely impaired due to the underlying nutritional deficiency?
A. Hexokinase
B. Transketolase
C. Lactate dehydrogenase
D. Glucose-6-phosphatase
E. Fructose-1,6-bisphosphatase
Answer: B. Transketolase
Rationale: Thiamine (vitamin B1) is required for transketolase, pyruvate dehydrogenase, α-
ketoglutarate dehydrogenase, and branched-chain α-ketoacid dehydrogenase. Thiamine
deficiency can cause Wernicke encephalopathy.
4.
A child has severe developmental delay, seizures, and a sweet-smelling odor to his urine.
Laboratory studies show elevated branched-chain amino acids. Which enzyme is deficient?
A. Phenylalanine hydroxylase
B. Homogentisate oxidase
C. Branched-chain α-ketoacid dehydrogenase
D. Cystathionine β-synthase
E. Tyrosinase
Answer: C. Branched-chain α-ketoacid dehydrogenase
Rationale: Maple syrup urine disease results from branched-chain α-ketoacid dehydrogenase
deficiency, causing accumulation of leucine, isoleucine, and valine.
5.
A 4-year-old child has developmental delay, seizures, and a musty body odor. Phenylalanine
levels are markedly elevated. Which treatment is appropriate?
A. High-protein diet
B. Phenylalanine-restricted diet
C. Galactose supplementation
D. Fructose supplementation
E. Methionine supplementation
Answer: B. Phenylalanine-restricted diet
,Rationale: Phenylketonuria is caused by phenylalanine hydroxylase deficiency or impaired
tetrahydrobiopterin metabolism. Treatment involves restricting phenylalanine and providing
tyrosine.
6.
A 25-year-old man has recurrent kidney stones and arthritis. Laboratory studies show increased
uric acid. He has a family history of similar disease. Which drug decreases uric acid production
by inhibiting xanthine oxidase?
A. Probenecid
B. Colchicine
C. Allopurinol
D. Indomethacin
E. Acetazolamide
Answer: C. Allopurinol
Rationale: Allopurinol inhibits xanthine oxidase, decreasing conversion of hypoxanthine and
xanthine to uric acid. It is useful for chronic gout and hyperuricemia.
7.
A child has intellectual disability, self-injurious behavior, dystonia, and hyperuricemia. Which
enzyme is deficient?
A. Adenosine deaminase
B. Hypoxanthine-guanine phosphoribosyltransferase
C. Xanthine oxidase
D. Purine nucleoside phosphorylase
E. Carbamoyl phosphate synthetase II
Answer: B. Hypoxanthine-guanine phosphoribosyltransferase
Rationale: Lesch-Nyhan syndrome is caused by HGPRT deficiency, resulting in impaired purine
salvage and increased uric acid production.
8.
A patient with anemia has a mutation affecting β-globin chains. Hemoglobin electrophoresis
shows increased HbA2 and HbF. Which condition is most likely?
A. Sickle cell disease
B. β-thalassemia
C. α-thalassemia
D. Hereditary spherocytosis
E. G6PD deficiency
, Answer: B. β-thalassemia
Rationale: β-thalassemia causes decreased β-globin synthesis. HbA2 and HbF are often
increased because δ- and γ-chain production compensates for reduced β chains.
9.
A 7-year-old boy develops jaundice and dark urine after taking a sulfonamide antibiotic. Blood
smear shows Heinz bodies and bite cells. Which enzyme deficiency is responsible?
A. Pyruvate kinase
B. Glucose-6-phosphate dehydrogenase
C. Hexokinase
D. Glutathione peroxidase
E. Superoxide dismutase
Answer: B. Glucose-6-phosphate dehydrogenase
Rationale: G6PD generates NADPH, which maintains glutathione in its reduced form.
Deficiency causes oxidative hemolysis after exposure to oxidant drugs, infections, or fava beans.
10.
A researcher studies a DNA mutation that does not alter the amino acid sequence of the resulting
protein. What type of mutation is this?
A. Missense
B. Nonsense
C. Frameshift
D. Silent
E. Splice-site
Answer: D. Silent
Rationale: A silent mutation changes a nucleotide but does not change the encoded amino acid
because multiple codons can specify the same amino acid.
Immunology
11.
A child has recurrent bacterial infections beginning at approximately 6 months of age.
Laboratory studies show markedly decreased immunoglobulin levels and absent mature B cells.
Which disorder is most likely?
A. DiGeorge syndrome
B. Bruton's agammaglobulinemia
C. Chronic granulomatous disease
VERIFIED QUSTION| GRADED A+|LATEST UPDATE 2026
Biochemistry & Genetics
1.
A 6-month-old boy is brought to the physician because of recurrent vomiting, lethargy, and
seizures after introduction of fruit juice into his diet. Laboratory studies show hypoglycemia and
elevated liver enzymes. Urine testing reveals reducing substances. Which enzyme deficiency is
most likely responsible?
A. Glucose-6-phosphatase
B. Fructokinase
C. Aldolase B
D. Galactose-1-phosphate uridyltransferase
E. Pyruvate carboxylase
Answer: C. Aldolase B
Rationale: Hereditary fructose intolerance is caused by aldolase B deficiency. Fructose-1-
phosphate accumulates after ingestion of fructose or sucrose, trapping phosphate and impairing
gluconeogenesis, leading to severe hypoglycemia.
2.
A newborn develops jaundice, hepatomegaly, vomiting, and failure to thrive after breastfeeding.
Laboratory studies show increased conjugated bilirubin and cataracts. Which enzyme is
deficient?
A. Galactokinase
B. Aldolase B
C. Galactose-1-phosphate uridyltransferase
D. UDP-glucose dehydrogenase
E. Glucose-6-phosphatase
Answer: C. Galactose-1-phosphate uridyltransferase
Rationale: Classic galactosemia results from GALT deficiency. Galactose-1-phosphate
accumulates and can cause liver dysfunction, jaundice, E. coli sepsis, and cataracts.
,3.
A patient with chronic alcoholism develops confusion, ophthalmoplegia, and ataxia. Which
enzyme is most likely impaired due to the underlying nutritional deficiency?
A. Hexokinase
B. Transketolase
C. Lactate dehydrogenase
D. Glucose-6-phosphatase
E. Fructose-1,6-bisphosphatase
Answer: B. Transketolase
Rationale: Thiamine (vitamin B1) is required for transketolase, pyruvate dehydrogenase, α-
ketoglutarate dehydrogenase, and branched-chain α-ketoacid dehydrogenase. Thiamine
deficiency can cause Wernicke encephalopathy.
4.
A child has severe developmental delay, seizures, and a sweet-smelling odor to his urine.
Laboratory studies show elevated branched-chain amino acids. Which enzyme is deficient?
A. Phenylalanine hydroxylase
B. Homogentisate oxidase
C. Branched-chain α-ketoacid dehydrogenase
D. Cystathionine β-synthase
E. Tyrosinase
Answer: C. Branched-chain α-ketoacid dehydrogenase
Rationale: Maple syrup urine disease results from branched-chain α-ketoacid dehydrogenase
deficiency, causing accumulation of leucine, isoleucine, and valine.
5.
A 4-year-old child has developmental delay, seizures, and a musty body odor. Phenylalanine
levels are markedly elevated. Which treatment is appropriate?
A. High-protein diet
B. Phenylalanine-restricted diet
C. Galactose supplementation
D. Fructose supplementation
E. Methionine supplementation
Answer: B. Phenylalanine-restricted diet
,Rationale: Phenylketonuria is caused by phenylalanine hydroxylase deficiency or impaired
tetrahydrobiopterin metabolism. Treatment involves restricting phenylalanine and providing
tyrosine.
6.
A 25-year-old man has recurrent kidney stones and arthritis. Laboratory studies show increased
uric acid. He has a family history of similar disease. Which drug decreases uric acid production
by inhibiting xanthine oxidase?
A. Probenecid
B. Colchicine
C. Allopurinol
D. Indomethacin
E. Acetazolamide
Answer: C. Allopurinol
Rationale: Allopurinol inhibits xanthine oxidase, decreasing conversion of hypoxanthine and
xanthine to uric acid. It is useful for chronic gout and hyperuricemia.
7.
A child has intellectual disability, self-injurious behavior, dystonia, and hyperuricemia. Which
enzyme is deficient?
A. Adenosine deaminase
B. Hypoxanthine-guanine phosphoribosyltransferase
C. Xanthine oxidase
D. Purine nucleoside phosphorylase
E. Carbamoyl phosphate synthetase II
Answer: B. Hypoxanthine-guanine phosphoribosyltransferase
Rationale: Lesch-Nyhan syndrome is caused by HGPRT deficiency, resulting in impaired purine
salvage and increased uric acid production.
8.
A patient with anemia has a mutation affecting β-globin chains. Hemoglobin electrophoresis
shows increased HbA2 and HbF. Which condition is most likely?
A. Sickle cell disease
B. β-thalassemia
C. α-thalassemia
D. Hereditary spherocytosis
E. G6PD deficiency
, Answer: B. β-thalassemia
Rationale: β-thalassemia causes decreased β-globin synthesis. HbA2 and HbF are often
increased because δ- and γ-chain production compensates for reduced β chains.
9.
A 7-year-old boy develops jaundice and dark urine after taking a sulfonamide antibiotic. Blood
smear shows Heinz bodies and bite cells. Which enzyme deficiency is responsible?
A. Pyruvate kinase
B. Glucose-6-phosphate dehydrogenase
C. Hexokinase
D. Glutathione peroxidase
E. Superoxide dismutase
Answer: B. Glucose-6-phosphate dehydrogenase
Rationale: G6PD generates NADPH, which maintains glutathione in its reduced form.
Deficiency causes oxidative hemolysis after exposure to oxidant drugs, infections, or fava beans.
10.
A researcher studies a DNA mutation that does not alter the amino acid sequence of the resulting
protein. What type of mutation is this?
A. Missense
B. Nonsense
C. Frameshift
D. Silent
E. Splice-site
Answer: D. Silent
Rationale: A silent mutation changes a nucleotide but does not change the encoded amino acid
because multiple codons can specify the same amino acid.
Immunology
11.
A child has recurrent bacterial infections beginning at approximately 6 months of age.
Laboratory studies show markedly decreased immunoglobulin levels and absent mature B cells.
Which disorder is most likely?
A. DiGeorge syndrome
B. Bruton's agammaglobulinemia
C. Chronic granulomatous disease
