COMPREHENSIVE OSTEOPATHIC MEDICAL SELF-ASSESSMENT EXAMINATION
(COMSAE) PHASE 1 FORM 114 COMPLETE PRACTICE EXAM QUESTIONS AND
ANSWERS | VERIFIED SOLUTIONS | UPDATED 2026/2027 STUDY GUIDE
Examiner/Administrator: National Board of Osteopathic Medical Examiners (NBOME)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPREHENSIVE OSTEOPATHIC
MEDICAL SELF-ASSESSMENT EXAMINATION
(COMSAE) PHASE 1 FORM 114
2026/2027 EDITION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPLETE PRACTICE EXAM
100 MULTIPLE-CHOICE QUESTIONS
EXACT OFFICIAL COUNT: 100 QUESTIONS
PASSING SCORE: 70%
TESTING TIME: 120 MINUTES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
NBOME-STYLE OSTEOPATHIC MEDICAL ASSESSMENT || ALIGNED WITH CURRENT
COMLEX-USA LEVEL 1 BLUEPRINTS || INTEGRATED BASIC SCIENCES & CLINICAL
REASONING || SYSTEMS-BASED MEDICAL REVIEW || 100% ORIGINAL VERIFIED
PRACTICE CONTENT || COMPREHENSIVE BOARD PREPARATION || OSTEOPATHIC
PRINCIPLES & PRACTICE INTEGRATION || PREPARED FOR PROFESSIONAL
EXAMINATION USE || UPDATED 2026/2027 ACADEMIC EDITION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
PROFESSIONAL
EXAMINATION MATERIAL
FOR EDUCATIONAL PREPARATION USE
,━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–10 → Biochemistry, Genetics & Molecular Medicine
Q1. A 3-year-old child presents with developmental delay, hepatomegaly, fasting
hypoglycemia, and elevated triglycerides. Liver biopsy demonstrates excessive
glycogen with normal structure. Deficiency of which enzyme most likely explains this
patient’s condition?
A. Glucose-6-phosphatase
B. Debranching enzyme
C. Branching enzyme
D. Lysosomal acid α-glucosidase
Correct Answer: 🔴 B. Debranching enzyme
Explanation: 🔹 The patient most likely has Cori disease (Glycogen Storage Disease Type
III), caused by deficiency of the glycogen debranching enzyme. Patients develop
hepatomegaly, fasting hypoglycemia, and accumulation of structurally normal glycogen.
Option A describes Von Gierke disease, which causes severe lactic acidosis and
hyperuricemia. Option C causes Andersen disease with abnormal glycogen structure and
cirrhosis. Option D refers to Pompe disease, characterized primarily by cardiomyopathy
and muscle weakness rather than hepatomegaly with fasting hypoglycemia.
Q2. A researcher studies a mutation causing defective post-translational hydroxylation
of proline residues in collagen. Which vitamin deficiency would most likely produce a
similar biochemical abnormality?
A. Vitamin A
B. Vitamin C
C. Vitamin D
D. Vitamin K
Correct Answer: 🔴 B. Vitamin C
Explanation: 🔹 Vitamin C serves as a cofactor for prolyl and lysyl hydroxylase enzymes
involved in collagen stabilization. Deficiency impairs collagen cross-linking, leading to
scurvy with bleeding gums, petechiae, and poor wound healing. Vitamin A primarily
,affects epithelial differentiation. Vitamin D regulates calcium metabolism. Vitamin K
participates in γ-carboxylation of clotting factors rather than collagen synthesis.
Q3. A newborn develops vomiting, lethargy, and seizures shortly after breastfeeding
begins. Laboratory studies reveal elevated galactose-1-phosphate levels. Which
enzyme deficiency is most likely present?
A. Galactokinase
B. Fructokinase
C. Galactose-1-phosphate uridyltransferase
D. Aldolase B
Correct Answer: 🔴 C. Galactose-1-phosphate uridyltransferase
Explanation: 🔹 Classic galactosemia results from galactose-1-phosphate
uridyltransferase deficiency. Toxic accumulation causes liver dysfunction, cataracts,
vomiting, and intellectual disability if untreated. Galactokinase deficiency causes infant
cataracts but less severe systemic disease. Fructokinase and aldolase B deficiencies are
associated with hereditary fructose disorders rather than galactose metabolism
abnormalities.
Q4. A patient with chronic alcoholism develops confusion, ophthalmoplegia, and gait
instability. Deficiency of which cofactor most likely impairs pyruvate dehydrogenase
activity in this condition?
A. Riboflavin
B. Thiamine
C. Biotin
D. Pyridoxine
Correct Answer: 🔴 B. Thiamine
Explanation: 🔹 Thiamine (vitamin B1) is an essential cofactor for pyruvate
dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain α-ketoacid
dehydrogenase, and transketolase. Deficiency leads to Wernicke encephalopathy
characterized by confusion, ophthalmoplegia, and ataxia. Riboflavin functions in FAD-
, dependent reactions. Biotin assists carboxylation reactions. Pyridoxine functions
primarily in amino acid metabolism.
Q5. A scientist identifies a mutation causing substitution of valine for glutamic acid in a
β-globin chain. Which structural protein abnormality results from this mutation?
A. Reduced α-helix formation
B. Increased collagen cross-linking
C. Hydrophobic polymerization during deoxygenation
D. Defective disulfide bond formation
Correct Answer: 🔴 C. Hydrophobic polymerization during deoxygenation
Explanation: 🔹 Sickle cell disease results from substitution of hydrophobic valine for
glutamic acid at position 6 of the β-globin chain. Under deoxygenated conditions,
hemoglobin S polymerizes, distorting erythrocytes into sickle shapes. This leads to vaso-
occlusion and hemolysis. The mutation does not primarily alter collagen or disulfide
bond formation.
Q6. A patient has elevated homocysteine levels and megaloblastic anemia. Deficiency
of which vitamin is most directly responsible for impaired methionine synthase
activity?
A. Folate
B. Vitamin B12
C. Vitamin E
D. Niacin
Correct Answer: 🔴 B. Vitamin B12
Explanation: 🔹 Methionine synthase requires vitamin B12 to convert homocysteine to
methionine. Deficiency causes elevated homocysteine and megaloblastic anemia due to
impaired DNA synthesis. Folate deficiency may produce similar hematologic findings but
B12 specifically acts as the cofactor in this reaction. Vitamin E deficiency causes
neurologic abnormalities related to oxidative damage. Niacin deficiency causes pellagra.
(COMSAE) PHASE 1 FORM 114 COMPLETE PRACTICE EXAM QUESTIONS AND
ANSWERS | VERIFIED SOLUTIONS | UPDATED 2026/2027 STUDY GUIDE
Examiner/Administrator: National Board of Osteopathic Medical Examiners (NBOME)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPREHENSIVE OSTEOPATHIC
MEDICAL SELF-ASSESSMENT EXAMINATION
(COMSAE) PHASE 1 FORM 114
2026/2027 EDITION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPLETE PRACTICE EXAM
100 MULTIPLE-CHOICE QUESTIONS
EXACT OFFICIAL COUNT: 100 QUESTIONS
PASSING SCORE: 70%
TESTING TIME: 120 MINUTES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
NBOME-STYLE OSTEOPATHIC MEDICAL ASSESSMENT || ALIGNED WITH CURRENT
COMLEX-USA LEVEL 1 BLUEPRINTS || INTEGRATED BASIC SCIENCES & CLINICAL
REASONING || SYSTEMS-BASED MEDICAL REVIEW || 100% ORIGINAL VERIFIED
PRACTICE CONTENT || COMPREHENSIVE BOARD PREPARATION || OSTEOPATHIC
PRINCIPLES & PRACTICE INTEGRATION || PREPARED FOR PROFESSIONAL
EXAMINATION USE || UPDATED 2026/2027 ACADEMIC EDITION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
PROFESSIONAL
EXAMINATION MATERIAL
FOR EDUCATIONAL PREPARATION USE
,━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–10 → Biochemistry, Genetics & Molecular Medicine
Q1. A 3-year-old child presents with developmental delay, hepatomegaly, fasting
hypoglycemia, and elevated triglycerides. Liver biopsy demonstrates excessive
glycogen with normal structure. Deficiency of which enzyme most likely explains this
patient’s condition?
A. Glucose-6-phosphatase
B. Debranching enzyme
C. Branching enzyme
D. Lysosomal acid α-glucosidase
Correct Answer: 🔴 B. Debranching enzyme
Explanation: 🔹 The patient most likely has Cori disease (Glycogen Storage Disease Type
III), caused by deficiency of the glycogen debranching enzyme. Patients develop
hepatomegaly, fasting hypoglycemia, and accumulation of structurally normal glycogen.
Option A describes Von Gierke disease, which causes severe lactic acidosis and
hyperuricemia. Option C causes Andersen disease with abnormal glycogen structure and
cirrhosis. Option D refers to Pompe disease, characterized primarily by cardiomyopathy
and muscle weakness rather than hepatomegaly with fasting hypoglycemia.
Q2. A researcher studies a mutation causing defective post-translational hydroxylation
of proline residues in collagen. Which vitamin deficiency would most likely produce a
similar biochemical abnormality?
A. Vitamin A
B. Vitamin C
C. Vitamin D
D. Vitamin K
Correct Answer: 🔴 B. Vitamin C
Explanation: 🔹 Vitamin C serves as a cofactor for prolyl and lysyl hydroxylase enzymes
involved in collagen stabilization. Deficiency impairs collagen cross-linking, leading to
scurvy with bleeding gums, petechiae, and poor wound healing. Vitamin A primarily
,affects epithelial differentiation. Vitamin D regulates calcium metabolism. Vitamin K
participates in γ-carboxylation of clotting factors rather than collagen synthesis.
Q3. A newborn develops vomiting, lethargy, and seizures shortly after breastfeeding
begins. Laboratory studies reveal elevated galactose-1-phosphate levels. Which
enzyme deficiency is most likely present?
A. Galactokinase
B. Fructokinase
C. Galactose-1-phosphate uridyltransferase
D. Aldolase B
Correct Answer: 🔴 C. Galactose-1-phosphate uridyltransferase
Explanation: 🔹 Classic galactosemia results from galactose-1-phosphate
uridyltransferase deficiency. Toxic accumulation causes liver dysfunction, cataracts,
vomiting, and intellectual disability if untreated. Galactokinase deficiency causes infant
cataracts but less severe systemic disease. Fructokinase and aldolase B deficiencies are
associated with hereditary fructose disorders rather than galactose metabolism
abnormalities.
Q4. A patient with chronic alcoholism develops confusion, ophthalmoplegia, and gait
instability. Deficiency of which cofactor most likely impairs pyruvate dehydrogenase
activity in this condition?
A. Riboflavin
B. Thiamine
C. Biotin
D. Pyridoxine
Correct Answer: 🔴 B. Thiamine
Explanation: 🔹 Thiamine (vitamin B1) is an essential cofactor for pyruvate
dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain α-ketoacid
dehydrogenase, and transketolase. Deficiency leads to Wernicke encephalopathy
characterized by confusion, ophthalmoplegia, and ataxia. Riboflavin functions in FAD-
, dependent reactions. Biotin assists carboxylation reactions. Pyridoxine functions
primarily in amino acid metabolism.
Q5. A scientist identifies a mutation causing substitution of valine for glutamic acid in a
β-globin chain. Which structural protein abnormality results from this mutation?
A. Reduced α-helix formation
B. Increased collagen cross-linking
C. Hydrophobic polymerization during deoxygenation
D. Defective disulfide bond formation
Correct Answer: 🔴 C. Hydrophobic polymerization during deoxygenation
Explanation: 🔹 Sickle cell disease results from substitution of hydrophobic valine for
glutamic acid at position 6 of the β-globin chain. Under deoxygenated conditions,
hemoglobin S polymerizes, distorting erythrocytes into sickle shapes. This leads to vaso-
occlusion and hemolysis. The mutation does not primarily alter collagen or disulfide
bond formation.
Q6. A patient has elevated homocysteine levels and megaloblastic anemia. Deficiency
of which vitamin is most directly responsible for impaired methionine synthase
activity?
A. Folate
B. Vitamin B12
C. Vitamin E
D. Niacin
Correct Answer: 🔴 B. Vitamin B12
Explanation: 🔹 Methionine synthase requires vitamin B12 to convert homocysteine to
methionine. Deficiency causes elevated homocysteine and megaloblastic anemia due to
impaired DNA synthesis. Folate deficiency may produce similar hematologic findings but
B12 specifically acts as the cofactor in this reaction. Vitamin E deficiency causes
neurologic abnormalities related to oxidative damage. Niacin deficiency causes pellagra.
