COMPREHENSIVE OSTEOPATHIC MEDICAL SELF-ASSESSMENT EXAMINATION
(COMSAE) PHASE 1 FORM 110 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 110
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 || BASIC SCIENCES INTEGRATION || SYSTEMS-
BASED CLINICAL APPLICATION || OSTEOPATHIC PRINCIPLES & PRACTICE ||
COMPREHENSIVE MEDICAL REVIEW GUIDE || HIGH-YIELD BOARD PREPARATION ||
100% ORIGINAL EDUCATIONAL CONTENT || VERIFIED ACADEMIC PRACTICE MATERIAL
|| PREPARED FOR PROFESSIONAL EXAMINATION USE
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–10 → Biochemistry, Genetics & Molecular Medicine
,Q1. A 3-month-old infant presents with vomiting, lethargy, hepatomegaly, and severe
fasting hypoglycemia. Laboratory studies reveal elevated free fatty acids with minimal
ketone production. Deficiency of which enzyme is the most likely underlying cause of
this presentation?
A. Hormone-sensitive lipase
B. Carnitine palmitoyltransferase I
C. Acetyl-CoA carboxylase
D. Medium-chain acyl-CoA dehydrogenase
Correct Answer: 🔴 B. Carnitine palmitoyltransferase I
Explanation: 🔹 Carnitine palmitoyltransferase I deficiency prevents long-chain fatty
acids from entering mitochondria for β-oxidation, leading to hypoketotic hypoglycemia
during fasting states. The inability to produce ketone bodies despite elevated fatty acids
is highly characteristic. Hormone-sensitive lipase deficiency would impair lipolysis rather
than mitochondrial transport. Acetyl-CoA carboxylase is involved in fatty acid synthesis,
not oxidation. Medium-chain acyl-CoA dehydrogenase deficiency also causes hypoketotic
hypoglycemia but typically presents with elevated medium-chain fatty acid metabolites
rather than isolated transport dysfunction.
Q2. A researcher identifies a mutation causing replacement of glycine with valine in a
structural protein composed predominantly of triple helices. Which clinical
manifestation is most likely associated with this mutation?
A. Fragile bones and blue sclerae
B. Hyperammonemia after high-protein meals
C. Progressive muscular dystrophy
D. Macrocytic anemia with neuropathy
Correct Answer: 🔴 A. Fragile bones and blue sclerae
Explanation: 🔹 Glycine is required every third residue in collagen triple helices.
Substitution mutations disrupt collagen stability and are classically associated with
osteogenesis imperfecta, characterized by brittle bones, blue sclerae, hearing loss, and
dentinogenesis imperfecta. Hyperammonemia suggests urea cycle disorders. Muscular
,dystrophy results from dystrophin abnormalities. Macrocytic anemia with neuropathy is
more consistent with vitamin B12 deficiency.
Q3. A patient with chronic alcoholism develops confusion, ophthalmoplegia, and gait
ataxia. Deficiency of thiamine most directly impairs which enzymatic process?
A. Conversion of succinate to fumarate
B. Oxidative decarboxylation of pyruvate
C. Hydrolysis of glycogen branches
D. Conversion of ribose-5-phosphate to PRPP
Correct Answer: 🔴 B. Oxidative decarboxylation of pyruvate
Explanation: 🔹 Thiamine pyrophosphate is a critical cofactor for pyruvate
dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain ketoacid
dehydrogenase, and transketolase. Deficiency impairs oxidative decarboxylation
reactions and ATP production, especially in neural tissue. Succinate dehydrogenase
requires FAD. Glycogen debranching enzymes do not require thiamine. PRPP synthesis
involves ribose phosphate pyrophosphokinase.
Q4. A 7-year-old child has recurrent respiratory infections and failure to thrive. Sweat
chloride testing is elevated. Which molecular defect most likely explains this disease?
A. Defective receptor tyrosine kinase signaling
B. Trinucleotide repeat expansion
C. Misfolded chloride channel degradation
D. Autoimmune destruction of exocrine tissue
Correct Answer: 🔴 C. Misfolded chloride channel degradation
Explanation: 🔹 Cystic fibrosis most commonly results from ΔF508 mutation in the CFTR
gene, producing a misfolded chloride channel degraded within the endoplasmic
reticulum. This impairs chloride transport and causes thick secretions in pulmonary and
gastrointestinal tissues. Receptor tyrosine kinase defects are unrelated. Trinucleotide
repeat disorders include Huntington disease and fragile X syndrome. Autoimmune
exocrine destruction describes Sjögren syndrome.
, Q5. A newborn develops seizures shortly after initiation of formula feeding. Laboratory
studies demonstrate markedly elevated ammonia with low blood urea nitrogen. Which
metabolic pathway is most directly impaired?
A. Glycolysis
B. Heme synthesis
C. Urea cycle
D. Pentose phosphate pathway
Correct Answer: 🔴 C. Urea cycle
Explanation: 🔹 Hyperammonemia with low BUN strongly indicates a urea cycle
disorder, commonly ornithine transcarbamylase deficiency. The inability to convert
ammonia into urea leads to neurotoxicity and cerebral edema. Glycolytic defects cause
lactic acidosis. Heme synthesis disorders cause porphyrias. Pentose phosphate defects
primarily impair NADPH generation.
Q6. A patient taking isoniazid develops peripheral neuropathy and sideroblastic
anemia. Supplementation with which vitamin would most likely prevent these findings?
A. Vitamin B1
B. Vitamin B6
C. Vitamin B9
D. Vitamin C
Correct Answer: 🔴 B. Vitamin B6
Explanation: 🔹 Isoniazid depletes pyridoxine (vitamin B6), leading to impaired
neurotransmitter synthesis and defective heme production. Pyridoxine supplementation
prevents neuropathy and sideroblastic anemia. Thiamine deficiency causes Wernicke-
Korsakoff syndrome. Folate deficiency causes megaloblastic anemia. Vitamin C
deficiency results in scurvy.
Q7. A scientist studies a toxin that irreversibly inhibits RNA polymerase II. Which
cellular process would be most immediately affected?
(COMSAE) PHASE 1 FORM 110 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 110
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 || BASIC SCIENCES INTEGRATION || SYSTEMS-
BASED CLINICAL APPLICATION || OSTEOPATHIC PRINCIPLES & PRACTICE ||
COMPREHENSIVE MEDICAL REVIEW GUIDE || HIGH-YIELD BOARD PREPARATION ||
100% ORIGINAL EDUCATIONAL CONTENT || VERIFIED ACADEMIC PRACTICE MATERIAL
|| PREPARED FOR PROFESSIONAL EXAMINATION USE
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–10 → Biochemistry, Genetics & Molecular Medicine
,Q1. A 3-month-old infant presents with vomiting, lethargy, hepatomegaly, and severe
fasting hypoglycemia. Laboratory studies reveal elevated free fatty acids with minimal
ketone production. Deficiency of which enzyme is the most likely underlying cause of
this presentation?
A. Hormone-sensitive lipase
B. Carnitine palmitoyltransferase I
C. Acetyl-CoA carboxylase
D. Medium-chain acyl-CoA dehydrogenase
Correct Answer: 🔴 B. Carnitine palmitoyltransferase I
Explanation: 🔹 Carnitine palmitoyltransferase I deficiency prevents long-chain fatty
acids from entering mitochondria for β-oxidation, leading to hypoketotic hypoglycemia
during fasting states. The inability to produce ketone bodies despite elevated fatty acids
is highly characteristic. Hormone-sensitive lipase deficiency would impair lipolysis rather
than mitochondrial transport. Acetyl-CoA carboxylase is involved in fatty acid synthesis,
not oxidation. Medium-chain acyl-CoA dehydrogenase deficiency also causes hypoketotic
hypoglycemia but typically presents with elevated medium-chain fatty acid metabolites
rather than isolated transport dysfunction.
Q2. A researcher identifies a mutation causing replacement of glycine with valine in a
structural protein composed predominantly of triple helices. Which clinical
manifestation is most likely associated with this mutation?
A. Fragile bones and blue sclerae
B. Hyperammonemia after high-protein meals
C. Progressive muscular dystrophy
D. Macrocytic anemia with neuropathy
Correct Answer: 🔴 A. Fragile bones and blue sclerae
Explanation: 🔹 Glycine is required every third residue in collagen triple helices.
Substitution mutations disrupt collagen stability and are classically associated with
osteogenesis imperfecta, characterized by brittle bones, blue sclerae, hearing loss, and
dentinogenesis imperfecta. Hyperammonemia suggests urea cycle disorders. Muscular
,dystrophy results from dystrophin abnormalities. Macrocytic anemia with neuropathy is
more consistent with vitamin B12 deficiency.
Q3. A patient with chronic alcoholism develops confusion, ophthalmoplegia, and gait
ataxia. Deficiency of thiamine most directly impairs which enzymatic process?
A. Conversion of succinate to fumarate
B. Oxidative decarboxylation of pyruvate
C. Hydrolysis of glycogen branches
D. Conversion of ribose-5-phosphate to PRPP
Correct Answer: 🔴 B. Oxidative decarboxylation of pyruvate
Explanation: 🔹 Thiamine pyrophosphate is a critical cofactor for pyruvate
dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain ketoacid
dehydrogenase, and transketolase. Deficiency impairs oxidative decarboxylation
reactions and ATP production, especially in neural tissue. Succinate dehydrogenase
requires FAD. Glycogen debranching enzymes do not require thiamine. PRPP synthesis
involves ribose phosphate pyrophosphokinase.
Q4. A 7-year-old child has recurrent respiratory infections and failure to thrive. Sweat
chloride testing is elevated. Which molecular defect most likely explains this disease?
A. Defective receptor tyrosine kinase signaling
B. Trinucleotide repeat expansion
C. Misfolded chloride channel degradation
D. Autoimmune destruction of exocrine tissue
Correct Answer: 🔴 C. Misfolded chloride channel degradation
Explanation: 🔹 Cystic fibrosis most commonly results from ΔF508 mutation in the CFTR
gene, producing a misfolded chloride channel degraded within the endoplasmic
reticulum. This impairs chloride transport and causes thick secretions in pulmonary and
gastrointestinal tissues. Receptor tyrosine kinase defects are unrelated. Trinucleotide
repeat disorders include Huntington disease and fragile X syndrome. Autoimmune
exocrine destruction describes Sjögren syndrome.
, Q5. A newborn develops seizures shortly after initiation of formula feeding. Laboratory
studies demonstrate markedly elevated ammonia with low blood urea nitrogen. Which
metabolic pathway is most directly impaired?
A. Glycolysis
B. Heme synthesis
C. Urea cycle
D. Pentose phosphate pathway
Correct Answer: 🔴 C. Urea cycle
Explanation: 🔹 Hyperammonemia with low BUN strongly indicates a urea cycle
disorder, commonly ornithine transcarbamylase deficiency. The inability to convert
ammonia into urea leads to neurotoxicity and cerebral edema. Glycolytic defects cause
lactic acidosis. Heme synthesis disorders cause porphyrias. Pentose phosphate defects
primarily impair NADPH generation.
Q6. A patient taking isoniazid develops peripheral neuropathy and sideroblastic
anemia. Supplementation with which vitamin would most likely prevent these findings?
A. Vitamin B1
B. Vitamin B6
C. Vitamin B9
D. Vitamin C
Correct Answer: 🔴 B. Vitamin B6
Explanation: 🔹 Isoniazid depletes pyridoxine (vitamin B6), leading to impaired
neurotransmitter synthesis and defective heme production. Pyridoxine supplementation
prevents neuropathy and sideroblastic anemia. Thiamine deficiency causes Wernicke-
Korsakoff syndrome. Folate deficiency causes megaloblastic anemia. Vitamin C
deficiency results in scurvy.
Q7. A scientist studies a toxin that irreversibly inhibits RNA polymerase II. Which
cellular process would be most immediately affected?
