A 12-year-old male presents to the pediatrician after two days of tea-colored urine which appeared to coincide with the first day of junior high football. He explains that he refused to go back to practice because he was humiliated by the other players due to his quick and excessive fatigue after a set of drills accompanied by pain in his muscles. A blood test revealed elevated creatine kinase and myoglobulin levels. A muscle biopsy was performed revealing large glycogen deposits and an enzyme histochemistry showed a lack of myophosphorylase activity. Which of the following reactions is not occurring in this individual?
Q22
A patient presents to the emergency room in an obtunded state. The patient is a known nurse within the hospital system and has no history of any medical problems. A finger stick blood glucose is drawn showing a blood glucose of 25 mg/dL.
The patient's daughter immediately arrives at the hospital stating that her mother has been depressed recently and that she found empty syringes in the bathroom at the mother's home. Which of the following is the test that will likely reveal the diagnosis?
Q23
A 12-month-old boy is brought to the physician by his mother for a well-child examination. He was delivered at term after an uncomplicated pregnancy. His mother says he is breastfeeding well. He is at the 50th percentile for height and 65th percentile for weight. Physical examination shows no abnormalities. Urinalysis shows 3+ reducing substances. Compared to a healthy infant, giving this patient apple juice to drink will result in increased activity of which of the following enzymes?
Q24
A 33-year-old woman, gravida 1, para 0, at 26 weeks' gestation comes to the physician for a routine prenatal examination. Her pregnancy has been uneventful. Physical examination shows a uterus consistent in size with a 26-week gestation. She is given an oral 50-g glucose load; 1 hour later, her serum glucose concentration is 116 mg/dL. Which of the following most likely occurred immediately after the entrance of glucose into the patient's pancreatic beta-cells?
Q25
A 3-month-old girl is brought to the emergency department by her parents after she appeared to have a seizure at home. On presentation, she no longer has convulsions though she is still noted to be lethargic. She was born through uncomplicated vaginal delivery and was not noted to have any abnormalities at the time of birth. Since then, she has been noted by her pediatrician to be falling behind in height and weight compared to similarly aged infants. Physical exam reveals an enlarged liver, and laboratory tests reveal a glucose of 38 mg/dL. Advanced testing shows that a storage molecule present in the cells of this patient has abnormally short outer chains. Which of the following enzymes is most likely defective in this patient?
Q26
A 63-year-old man is brought in by ambulance after a bar fight. Witnesses report that he is a bar regular and often drinks several shots of hard liquor throughout the night. The emergency department recognizes him as a local homeless man with a long history of alcohol abuse. During the initial workup in the ED, he has a prolonged seizure and dies. An autopsy is performed that shows an enlarged heart with severe calcified atherosclerotic coronary arteries. Evaluation of his brain shows atrophic mammillary bodies with brown-tan discoloration. Which of the following tests would have most likely produced an abnormal result in vivo with respect to his nervous system findings on autopsy?
Q27
A 3-month-old boy is brought to the emergency department by his mother after a seizure at home. The mother is not sure how long the seizure lasted, but says that the boy was unresponsive and had episodes of stiffness and jerking of his extremities throughout the episode. The mother states that the boy has not seemed himself for the past several weeks and has been fussy with feeds. He does not sleep through the night. He has not had any recent infections or sick contacts.
On exam, the boy is lethargic. His temperature is 99.5°F (37.5°C), blood pressure is 70/40 mmHg, and pulse is 120/min. He has no murmurs and his lungs are clear to auscultation bilaterally. His abdomen appears protuberant, and his liver span is measured at 4.5 cm below the costal margin. Additionally, the boy has abnormally enlarged cheeks. A finger stick in the ED reveals a blood glucose level of 35 mg/dL. What would this patient’s response to a fasting-state glucagon stimulation test most likely be, and what enzyme defect does he have?
Q28
A newborn infant presents with severe weakness. He was born to a G1P1 mother at 40 weeks gestation with the pregnancy attended by a midwife. The mother's past medical history is unremarkable. She took a prenatal vitamin and folic acid throughout the pregnancy. Since birth, the child has had trouble breastfeeding despite proper counseling. He also has had poor muscle tone and a weak cry. His temperature is 99.5°F (37.5°C), blood pressure is 57/38 mmHg, pulse is 150/min, respirations are 37/min, and oxygen saturation is 96% on room air. Physical exam reveals poor muscle tone. The patient's sucking reflex is weak, and an enlarged tongue is noted. An ultrasound is performed, and is notable for hypertrophy of the myocardium. Which of the following is the most likely diagnosis?
Q29
A 7-year-old boy and the rest of his family visit a physician for a physical after migrating to the United States. His mother reports that her son is always fatigued and has no energy to play like the other kids in their remote village in Nigeria. He was born at 39 weeks via spontaneous vaginal delivery and is meeting all developmental milestones. He is behind on most of his vaccines, and they develop a plan to get him caught up. On examination, the boy presents with jaundice, mild hepatomegaly, and tachycardia. A CBC with manual differential reveals atypical appearing red blood cells. The physician takes time to review the lab work results with the mother, and he discusses her son’s diagnosis. It is expected that one molecule at the biochemical level should be high. Which of the following best describes this molecule and its significance in this patient?
Q30
A 15-year-old boy comes to the physician because of severe muscle cramps and pain for 3 months. He first noticed these symptoms while attending tryouts for the high school football team. Since then, he becomes easily fatigued and has severe muscle pain and swelling after 10 minutes of playing. However, after a brief period of rest, the symptoms improve, and he is able to return to the game. Two days ago, he had an episode of reddish-brown urine after playing football. There is no family history of serious illness. He appears healthy. Vital signs are within normal limits. Physical and neurological examinations show no abnormalities. Serum creatine kinase concentration is 333 U/L. Urinalysis shows:
Blood 2+
Protein negative
Glucose negative
RBC negative
WBC 1–2/hpf
Which of the following is the most likely cause of this patient's symptoms?
Glycolysis US Medical PG Practice Questions and MCQs
Question 21: A 12-year-old male presents to the pediatrician after two days of tea-colored urine which appeared to coincide with the first day of junior high football. He explains that he refused to go back to practice because he was humiliated by the other players due to his quick and excessive fatigue after a set of drills accompanied by pain in his muscles. A blood test revealed elevated creatine kinase and myoglobulin levels. A muscle biopsy was performed revealing large glycogen deposits and an enzyme histochemistry showed a lack of myophosphorylase activity. Which of the following reactions is not occurring in this individual?
A. Cleaving alpha-1,6 glycosidic bonds from glycogen
B. Creating alpha-1,6 glycosidic bonds in glycogen
C. Breaking down glycogen to glucose-1-phosphate (Correct Answer)
D. Converting glucose-6-phosphate to glucose
E. Converting galactose to galactose-1-phosphate
Explanation: ***Breaking down glycogen to glucose-1-phosphate***
- The patient's symptoms (muscle pain, quick fatigue during exercise, tea-colored urine indicating **rhabdomyolysis**) and laboratory findings (**elevated creatine kinase and myoglobin**, **large glycogen deposits** in muscle, and **lack of myophosphorylase activity**) are classic for **McArdle disease (Glycogen Storage Disease Type V).**
- **Myophosphorylase** (also known as **glycogen phosphorylase**) is the enzyme responsible for breaking down glycogen into **glucose-1-phosphate** in muscle, so this reaction is severely impaired.
*Cleaving alpha-1,6 glycosidic bonds from glycogen*
- This reaction is catalyzed by the **debranching enzyme** (specifically, its **oligo-1,6-glucosidase** activity), not myophosphorylase.
- The debranching enzyme is crucial for completely breaking down glycogen, but its deficiency would lead to different clinical and histopathological findings (e.g., accumulation of **dextrin-like structures**).
*Creating alpha-1,6 glycosidic bonds in glycogen*
- This is the function of the **branching enzyme**, which introduces branches into the glycogen structure.
- This process is part of **glycogen synthesis**, not degradation, and is not directly affected by myophosphorylase deficiency.
*Converting glucose-6-phosphate to glucose*
- This reaction primarily occurs in the liver and kidneys, catalyzed by **glucose-6-phosphatase**, to release glucose into the bloodstream.
- While muscle cells can produce glucose-6-phosphate from glycogen, they lack glucose-6-phosphatase, so they cannot release free glucose into the blood. This reaction is irrelevant to the primary defect here.
*Converting galactose to galactose-1-phosphate*
- This is an initial step in **galactose metabolism**, catalyzed by **galactokinase**.
- This metabolic pathway is entirely separate from glycogen metabolism and is not implicated in McArdle disease.
Question 22: A patient presents to the emergency room in an obtunded state. The patient is a known nurse within the hospital system and has no history of any medical problems. A finger stick blood glucose is drawn showing a blood glucose of 25 mg/dL.
The patient's daughter immediately arrives at the hospital stating that her mother has been depressed recently and that she found empty syringes in the bathroom at the mother's home. Which of the following is the test that will likely reveal the diagnosis?
A. Fasting blood glucose
B. Urine metanephrines
C. Genetic testing
D. 24 hr cortisol
E. C-peptide level (Correct Answer)
Explanation: ***C-peptide level***
- A **low C-peptide level** in the presence of **hypoglycemia** and high insulin levels confirms the diagnosis of **exogenous insulin administration** (factitious hypoglycemia).
- **C-peptide** is cleaved from **proinsulin** in equimolar amounts with endogenous insulin, making it an excellent marker to differentiate endogenous insulin production from exogenous insulin injection.
- In this case: **Low C-peptide + High insulin + Hypoglycemia** = exogenous insulin administration.
*Fasting blood glucose*
- The patient already has documented **hypoglycemia (25 mg/dL)**, so an additional fasting blood glucose test would not provide further diagnostic information about the **cause** of hypoglycemia.
- A single fasting blood glucose level indicates current glucose status but **does not differentiate** between endogenous insulin overproduction (insulinoma) and exogenous insulin administration.
*Urine metanephrines*
- **Urine metanephrines** are used to diagnose **pheochromocytoma**, a catecholamine-secreting tumor of the adrenal medulla.
- Pheochromocytoma presents with **hypertension**, palpitations, headaches, and diaphoresis—**not hypoglycemia**.
- This test is not relevant to the differential diagnosis of hypoglycemia.
*Genetic testing*
- **Genetic testing** might be considered for rare hereditary causes of hypoglycemia, such as congenital hyperinsulinism or genetic insulinoma syndromes (e.g., MEN1).
- Given the clinical context (depressed nurse with access to insulin and empty syringes found at home), **exogenous insulin administration** is far more likely than a genetic condition.
- Genetic testing is not the appropriate initial diagnostic step in this scenario.
*24 hr cortisol*
- A **24-hour urinary cortisol** test is used to diagnose **Cushing's syndrome** (cortisol excess), not hypoglycemia.
- While **adrenal insufficiency** (cortisol deficiency) can cause hypoglycemia, it typically presents with **hypotension**, **hyponatremia**, **hyperkalemia**, and **hyperpigmentation**—features not described in this case.
- The clinical presentation strongly suggests insulin-related hypoglycemia rather than adrenal insufficiency.
Question 23: A 12-month-old boy is brought to the physician by his mother for a well-child examination. He was delivered at term after an uncomplicated pregnancy. His mother says he is breastfeeding well. He is at the 50th percentile for height and 65th percentile for weight. Physical examination shows no abnormalities. Urinalysis shows 3+ reducing substances. Compared to a healthy infant, giving this patient apple juice to drink will result in increased activity of which of the following enzymes?
A. Galactokinase
B. α-1,6-glucosidase
C. Fructokinase
D. Aldolase B
E. Hexokinase (Correct Answer)
Explanation: ***Hexokinase***
- This patient has **essential fructosuria** (fructokinase deficiency), a **benign condition** presenting with positive reducing substances in urine but **normal growth and development** (unlike galactosemia, which causes failure to thrive).
- **Apple juice** contains high concentrations of both **fructose** and **glucose**. Since fructokinase is deficient, the patient cannot metabolize fructose efficiently, and it spills into the urine.
- However, the **glucose component** of apple juice will be metabolized normally via **hexokinase**, which phosphorylates glucose to glucose-6-phosphate. Increased glucose intake leads to **increased hexokinase activity**.
*Galactokinase*
- **Galactokinase** phosphorylates galactose to galactose-1-phosphate in the first step of galactose metabolism.
- This patient's condition involves **fructose metabolism**, not galactose metabolism. Apple juice contains primarily glucose and fructose, not galactose.
- Galactokinase activity would not be significantly affected by apple juice consumption.
*α-1,6-glucosidase*
- This **debranching enzyme** is involved in **glycogenolysis** (breakdown of glycogen at branch points).
- Deficiency causes **Cori disease (Type III Glycogen Storage Disease)**.
- This enzyme is not involved in the metabolism of dietary sugars from apple juice and would not show increased activity.
*Fructokinase*
- **Fructokinase** phosphorylates fructose to fructose-1-phosphate in the first step of fructose metabolism.
- This patient has **essential fructosuria** due to **fructokinase deficiency**, so this enzyme has **reduced or absent activity**, not increased activity.
- The positive reducing substances in urine represent unmetabolized fructose accumulating due to this deficiency.
*Aldolase B*
- **Aldolase B** cleaves fructose-1-phosphate to dihydroxyacetone phosphate and glyceraldehyde in the second step of fructose metabolism.
- Deficiency causes **hereditary fructose intolerance** (HFI), which presents with severe symptoms (vomiting, hypoglycemia, hepatomegaly, failure to thrive) when fructose is consumed—unlike this asymptomatic patient.
- Since fructokinase is deficient in this patient, **fructose-1-phosphate is not produced**, so aldolase B would not show increased activity.
Question 24: A 33-year-old woman, gravida 1, para 0, at 26 weeks' gestation comes to the physician for a routine prenatal examination. Her pregnancy has been uneventful. Physical examination shows a uterus consistent in size with a 26-week gestation. She is given an oral 50-g glucose load; 1 hour later, her serum glucose concentration is 116 mg/dL. Which of the following most likely occurred immediately after the entrance of glucose into the patient's pancreatic beta-cells?
A. Closure of membranous potassium channels
B. Generation of adenosine triphosphate (Correct Answer)
C. Increased expression of hexokinase I mRNA
D. Exocytosis of insulin granules
E. Depolarization of beta-cell membrane
Explanation: ***Generation of adenosine triphosphate***
- Immediately after glucose enters pancreatic beta-cells via **GLUT2 transporters**, it is phosphorylated by **glucokinase (hexokinase IV)** to glucose-6-phosphate.
- This glucose is then metabolized through **glycolysis** and the **Krebs cycle**, leading to the generation of **ATP**.
- This increase in intracellular **ATP/ADP ratio** is the **primary signal** that links glucose metabolism to insulin secretion.
- Among the listed options, ATP generation is the **earliest event** that occurs.
*Closure of membranous potassium channels*
- The elevated **ATP** levels from glucose metabolism lead to the closure of **ATP-sensitive potassium (K-ATP) channels**.
- This closure is a subsequent event that depends on the increased ATP/ADP ratio, not an immediate consequence of glucose entry.
*Increased expression of hexokinase I mRNA*
- While **glucokinase (hexokinase IV)** activity is crucial for glucose phosphorylation in beta-cells, increased mRNA expression is a **long-term adaptive response** requiring transcription and translation.
- The immediate response involves the existing enzyme converting glucose to **glucose-6-phosphate**, followed by ATP generation.
*Exocytosis of insulin granules*
- **Insulin granule exocytosis** is the final step in insulin release, occurring after a cascade of events: ATP generation → K-ATP channel closure → membrane depolarization → calcium influx.
- This event is a *downstream consequence*, not an immediate result of glucose entering the cell.
*Depolarization of beta-cell membrane*
- **Membrane depolarization** follows the closure of ATP-sensitive potassium channels, which then leads to the opening of **voltage-gated calcium channels**.
- This is a subsequent event that depends on the initial ATP generation and K-ATP channel closure.
Question 25: A 3-month-old girl is brought to the emergency department by her parents after she appeared to have a seizure at home. On presentation, she no longer has convulsions though she is still noted to be lethargic. She was born through uncomplicated vaginal delivery and was not noted to have any abnormalities at the time of birth. Since then, she has been noted by her pediatrician to be falling behind in height and weight compared to similarly aged infants. Physical exam reveals an enlarged liver, and laboratory tests reveal a glucose of 38 mg/dL. Advanced testing shows that a storage molecule present in the cells of this patient has abnormally short outer chains. Which of the following enzymes is most likely defective in this patient?
A. Debranching enzyme (Correct Answer)
B. Hepatic phosphorylase
C. Glucose-6-phosphatase
D. Muscle phosphorylase
E. Branching enzyme
Explanation: ***Debranching enzyme***
- The presence of **abnormally short outer chains** in a storage molecule, along with **hypoglycemia** and **hepatomegaly**, strongly suggests a defect in the **debranching enzyme** (Type III Glycogen Storage Disease or Cori/Forbes disease). This enzyme is responsible for breaking down the α-1,6 glycosidic bonds at the branch points of glycogen.
- Deficiency leads to the accumulation of glycogen with **short branches**, affecting both liver and muscle.
*Hepatic phosphorylase*
- A defect in **hepatic phosphorylase** (Type VI Glycogen Storage Disease or Hers' disease) leads to similar symptoms like **hepatomegaly** and **hypoglycemia**.
- However, the glycogen structure would be normal, not characterized by abnormally short outer chains.
*Glucose-6-phosphatase*
- A deficiency in **glucose-6-phosphatase** (Type I Glycogen Storage Disease or Von Gierke's disease) leads to severe **hypoglycemia**, **hepatomegaly**, and often **renal enlargement**.
- Glycogen structure in this condition is typically normal, with **increased hepatic glycogen stores**.
*Muscle phosphorylase*
- A deficiency in **muscle phosphorylase** (Type V Glycogen Storage Disease or McArdle's disease) primarily affects skeletal muscle function, causing **muscle cramping**, pain, and **fatigue during exercise**.
- It does not typically present with severe **hypoglycemia** or **hepatomegaly** because the liver enzyme is unaffected.
*Branching enzyme*
- A defect in the **branching enzyme** (Type IV Glycogen Storage Disease or Andersen's disease) results in glycogen with **abnormally long unbranched chains** and fewer branch points.
- This typically leads to **cirrhosis** and liver failure, and while hypoglycemia can occur, the characteristic glycogen structure is the opposite of what is described in the patient.
Question 26: A 63-year-old man is brought in by ambulance after a bar fight. Witnesses report that he is a bar regular and often drinks several shots of hard liquor throughout the night. The emergency department recognizes him as a local homeless man with a long history of alcohol abuse. During the initial workup in the ED, he has a prolonged seizure and dies. An autopsy is performed that shows an enlarged heart with severe calcified atherosclerotic coronary arteries. Evaluation of his brain shows atrophic mammillary bodies with brown-tan discoloration. Which of the following tests would have most likely produced an abnormal result in vivo with respect to his nervous system findings on autopsy?
A. Aldolase B activity
B. Rapid fluorescent spot test
C. Erythrocyte transketolase activity (Correct Answer)
D. CSF IgG protein
E. Serum methylmalonic acid
Explanation: ***Erythrocyte transketolase activity***
- The patient's history of **chronic alcohol abuse**, prolonged seizure, and post-mortem findings of **atrophic mammillary bodies with brown-tan discoloration** are characteristic of **Wernicke-Korsakoff syndrome**, caused by **thiamine (vitamin B1) deficiency**.
- **Transketolase** is a thiamine-dependent enzyme involved in the **pentose phosphate pathway**; its activity in erythrocytes would be **decreased** in thiamine deficiency.
*Aldolase B activity*
- **Aldolase B** is an enzyme involved in **fructose metabolism**, and its deficiency is associated with **hereditary fructose intolerance**.
- There is no clinical or pathological evidence in this case to suggest a disorder of fructose metabolism.
*Rapid fluorescent spot test*
- This test is used to screen for **glucose-6-phosphate dehydrogenase (G6PD) deficiency**, a condition characterized by **hemolytic anemia** triggered by certain drugs or infections.
- While chronic alcohol abuse can lead to various hematologic abnormalities, there is no direct link between G6PD deficiency and Wernicke-Korsakoff syndrome or the patient's specific presentation.
*CSF IgG protein*
- Elevated **CSF IgG protein** is typically seen in inflammatory or demyelinating conditions of the central nervous system, such as **multiple sclerosis** or certain infections.
- This finding is not directly associated with thiamine deficiency or alcoholic encephalopathy.
*Serum methylmalonic acid*
- Elevated **serum methylmalonic acid** is a sensitive indicator of **vitamin B12 deficiency**, which can cause neurological symptoms.
- While alcoholics can have various nutritional deficiencies, the specific brain pathology described (mammillary body atrophy) is characteristic of thiamine deficiency, not vitamin B12 deficiency.
Question 27: A 3-month-old boy is brought to the emergency department by his mother after a seizure at home. The mother is not sure how long the seizure lasted, but says that the boy was unresponsive and had episodes of stiffness and jerking of his extremities throughout the episode. The mother states that the boy has not seemed himself for the past several weeks and has been fussy with feeds. He does not sleep through the night. He has not had any recent infections or sick contacts.
On exam, the boy is lethargic. His temperature is 99.5°F (37.5°C), blood pressure is 70/40 mmHg, and pulse is 120/min. He has no murmurs and his lungs are clear to auscultation bilaterally. His abdomen appears protuberant, and his liver span is measured at 4.5 cm below the costal margin. Additionally, the boy has abnormally enlarged cheeks. A finger stick in the ED reveals a blood glucose level of 35 mg/dL. What would this patient’s response to a fasting-state glucagon stimulation test most likely be, and what enzyme defect does he have?
A. Rise in plasma glucose; alpha-1,4-glucosidase
B. Rise in plasma glucose; liver phosphorylase
C. Rise in plasma glucose; glycogen debranching enzyme
D. No change in plasma glucose; glucose-6-phosphatase (Correct Answer)
E. Rise in plasma glucose; muscle phosphorylase
Explanation: ***No change in plasma glucose; glucose-6-phosphatase***
- The clinical presentation, including **hypoglycemia** (35 mg/dL), **hepatomegaly** (liver span 4.5 cm below costal margin), and **enlarged cheeks** (due to fat deposition), is classic for **Glycogen Storage Disease Type I (von Gierke disease)**. This condition is caused by a deficiency in **glucose-6-phosphatase**.
- In von Gierke disease, the body cannot convert **glycogen to glucose** or perform **gluconeogenesis** efficiently. Therefore, a **glucagon stimulation test** (which typically promotes glycogenolysis and gluconeogenesis to raise blood glucose) would show **no change** in plasma glucose levels because the final enzyme in this pathway, glucose-6-phosphatase, is deficient.
*Rise in plasma glucose; alpha-1,4-glucosidase*
- A deficiency in **alpha-1,4-glucosidase** (acid maltase) causes **Glycogen Storage Disease Type II (Pompe disease)**, which primarily affects muscles and the heart.
- While it can present with profound hypotonia and cardiomegaly, it typically **does not cause hypoglycemia** or marked hepatomegaly with fasting, and a glucagon test would likely show a rise in plasma glucose as the enzymes involved in glucose production are intact.
*Rise in plasma glucose; liver phosphorylase*
- A deficiency in **liver phosphorylase** causes **Glycogen Storage Disease Type VI (Hers disease)**. This can lead to hepatomegaly and hypoglycemia.
- However, in Hers disease, the **glucose-6-phosphatase** enzyme is functional, so a glucagon stimulation test would eventually lead to a **rise in plasma glucose** once glycogen breakdown products reach this final step.
*Rise in plasma glucose; glycogen debranching enzyme*
- A deficiency in **glycogen debranching enzyme** causes **Glycogen Storage Disease Type III (Cori disease)**. This condition also presents with hepatomegaly and hypoglycemia, similar to von Gierke disease.
- However, because the **glucose-6-phosphatase** enzyme is functional, a glucagon stimulation test would eventually show a **rise in plasma glucose**, albeit a blunted or delayed rise, after partial glycogenolysis occurs.
*No change in plasma glucose; muscle phosphorylase*
- A deficiency in **muscle phosphorylase** causes **Glycogen Storage Disease Type V (McArdle disease)**, which primarily affects skeletal muscles.
- Patients typically present with **exercise intolerance**, muscle cramps, and myoglobinuria, and do not experience **hypoglycemia** or hepatomegaly. The liver enzymes for glucose production would be intact, so a glucagon test would show a rise in plasma glucose.
Question 28: A newborn infant presents with severe weakness. He was born to a G1P1 mother at 40 weeks gestation with the pregnancy attended by a midwife. The mother's past medical history is unremarkable. She took a prenatal vitamin and folic acid throughout the pregnancy. Since birth, the child has had trouble breastfeeding despite proper counseling. He also has had poor muscle tone and a weak cry. His temperature is 99.5°F (37.5°C), blood pressure is 57/38 mmHg, pulse is 150/min, respirations are 37/min, and oxygen saturation is 96% on room air. Physical exam reveals poor muscle tone. The patient's sucking reflex is weak, and an enlarged tongue is noted. An ultrasound is performed, and is notable for hypertrophy of the myocardium. Which of the following is the most likely diagnosis?
A. Acid maltase deficiency (Correct Answer)
B. Familial hypertrophic cardiomyopathy
C. Clostridium tetani infection
D. Spinal muscular atrophy type I disease
E. Clostridium botulinum infection
Explanation: ***Acid maltase deficiency***
- This condition is also known as **Pompe disease**. It is a **lysosomal storage disease** that presents in infancy with **cardiomegaly**, **macroglossia**, **hypotonia**, and **respiratory failure**, all of which are consistent with the patient's presentation.
- The deficiency in **acid alpha-glucosidase (acid maltase)** leads to glycogen accumulation in lysosomes, particularly in muscle cells, causing impaired muscle function, including the heart.
*Familial hypertrophic cardiomyopathy*
- While it causes **myocardial hypertrophy**, it typically does **not present with profound generalized hypotonia, macroglossia, or feeding difficulties** as the primary symptoms in infancy.
- This condition is usually due to **sarcomeric protein mutations** and lacks the widespread systemic muscle involvement seen in Pompe disease.
*Clostridium tetani infection*
- This infection causes **tetanus**, characterized by **severe muscle spasms, trismus (lockjaw), and opisthotonus**, rather than hypotonia and weakness.
- It would also typically involve a history of a **puncture wound or contaminated injury**, which is not mentioned.
*Spinal muscular atrophy type I disease*
- This is characterized by **severe hypotonia** and **muscle weakness** due to the degeneration of anterior horn cells.
- However, **cardiomegaly and macroglossia are not typical features** of spinal muscular atrophy.
*Clostridium botulinum infection*
- This infection causes **flaccid paralysis** and weakness, usually presenting with **constipation**, **weak cry**, and **difficulty feeding**, by preventing acetylcholine release at neuromuscular junctions.
- However, **cardiomyopathy and macroglossia are not characteristic** of botulism.
Question 29: A 7-year-old boy and the rest of his family visit a physician for a physical after migrating to the United States. His mother reports that her son is always fatigued and has no energy to play like the other kids in their remote village in Nigeria. He was born at 39 weeks via spontaneous vaginal delivery and is meeting all developmental milestones. He is behind on most of his vaccines, and they develop a plan to get him caught up. On examination, the boy presents with jaundice, mild hepatomegaly, and tachycardia. A CBC with manual differential reveals atypical appearing red blood cells. The physician takes time to review the lab work results with the mother, and he discusses her son’s diagnosis. It is expected that one molecule at the biochemical level should be high. Which of the following best describes this molecule and its significance in this patient?
A. Physiological; found in the mitochondrial intermembrane space
B. Pathological; an intermediate of glycolysis (Correct Answer)
C. Pathological; an intermediate of the Krebs cycle
D. Physiological; an intermediate of glycolysis
E. Physiological; an intermediate of gluconeogenesis
Explanation: ***Pathological; an intermediate of glycolysis***
- The patient's symptoms (fatigue, jaundice, hepatomegaly, tachycardia, atypical red blood cells) are consistent with **chronic hemolytic anemia**, likely due to **pyruvate kinase deficiency**, a genetic condition more common in populations from Africa and the Mediterranean.
- In **pyruvate kinase deficiency**, the enzyme that converts phosphoenolpyruvate (PEP) to pyruvate is deficient, leading to impaired ATP production in red blood cells.
- This causes a compensatory increase in **2,3-Bisphosphoglycerate (2,3-BPG)** through the Rapoport-Luebering shunt, a side pathway of glycolysis that diverts 1,3-BPG to form 2,3-BPG.
- Elevated **2,3-BPG is pathological** in this context and is an **intermediate associated with glycolysis**, making this the correct answer.
*Physiological; found in the mitochondrial intermembrane space*
- This option refers to molecules like **cytochrome c** found in the mitochondrial intermembrane space during normal oxidative phosphorylation.
- Red blood cells lack mitochondria, so this is not relevant to the pathology described.
- The clinical presentation indicates a pathological state, not normal physiology.
*Pathological; an intermediate of the Krebs cycle*
- The Krebs cycle occurs in mitochondria, which **mature red blood cells lack**.
- The hemolytic anemia with atypical red blood cells specifically points to a defect in **red blood cell glycolysis**, not the Krebs cycle.
- This option is incorrect because the pathology involves glycolysis, not the Krebs cycle.
*Physiological; an intermediate of glycolysis*
- While 2,3-BPG is technically an intermediate related to glycolysis, its **markedly elevated level in this patient is pathological**, not physiological.
- The molecule is high due to disease (pyruvate kinase deficiency), not normal metabolic function.
- The context clearly describes a pathological condition requiring the molecule to be abnormally elevated.
*Physiological; an intermediate of gluconeogenesis*
- Gluconeogenesis occurs primarily in the liver and kidneys, not in red blood cells.
- Red blood cells rely exclusively on glycolysis for ATP production and do not perform gluconeogenesis.
- The condition is pathological, not a normal physiological state.
Question 30: A 15-year-old boy comes to the physician because of severe muscle cramps and pain for 3 months. He first noticed these symptoms while attending tryouts for the high school football team. Since then, he becomes easily fatigued and has severe muscle pain and swelling after 10 minutes of playing. However, after a brief period of rest, the symptoms improve, and he is able to return to the game. Two days ago, he had an episode of reddish-brown urine after playing football. There is no family history of serious illness. He appears healthy. Vital signs are within normal limits. Physical and neurological examinations show no abnormalities. Serum creatine kinase concentration is 333 U/L. Urinalysis shows:
Blood 2+
Protein negative
Glucose negative
RBC negative
WBC 1–2/hpf
Which of the following is the most likely cause of this patient's symptoms?
A. CTG repeat in the DMPK gene
B. Myophosphorylase deficiency (Correct Answer)
C. Dystrophin gene mutation
D. Thyroid hormone deficiency
E. Acid maltase deficiency
Explanation: ***Myophosphorylase deficiency***
- This condition (also known as **McArdle disease**) presents with **exercise-induced muscle cramps, pain, and fatigue** immediately after initiating activity, with a "second wind" phenomenon where symptoms improve after resting.
- The elevated **creatine kinase** and **reddish-brown urine** (indicating **myoglobinuria** due to rhabdomyolysis) are classic findings after strenuous activity in this glycogen storage disorder.
*CTG repeat in the DMPK gene*
- This describes **myotonic dystrophy type 1**, which presents with **myotonia** (delayed muscle relaxation), muscle weakness, and often involves multiple organ systems.
- While it causes muscle weakness, it does not typically present with acute, exercise-induced pain, cramping, and rhabdomyolysis in this manner.
*Dystrophin gene mutation*
- This is characteristic of **Duchenne or Becker muscular dystrophy**, which are progressive muscle weakness disorders.
- They typically cause **progressive proximal muscle weakness** and atrophy, not acute, intermittent, exercise-induced pain and cramping with a "second wind" phenomenon.
*Thyroid hormone deficiency*
- **Hypothyroidism** can cause muscle cramps, weakness, and elevated creatine kinase, but these symptoms are usually chronic and progressive, not acutely exercise-induced with improvement after a short rest.
- It would also present with other systemic symptoms like fatigue, weight gain, and cold intolerance, which are not described.
*Acid maltase deficiency*
- Also known as **Pompe disease**, this is a glycogen storage disorder that primarily affects infants and can present in adults with **proximal muscle weakness**, respiratory insufficiency, and cardiac involvement.
- It does not typically present with acute, exercise-induced muscle cramps, pain, and rhabdomyolysis followed by a "second wind" phenomenon like McArdle disease.
