A 46-year-old man comes to the physician for a follow-up examination. He has type 2 diabetes mellitus and hypertension. Current medications include metformin and lisinopril. He reports that he has adhered to his diet and medication regimen. His hemoglobin A1c is 8.6%. Insulin glargine is added to his medication regimen. Which of the following sets of changes is most likely to occur in response to this new medication?
$$$ Glycolysis %%% Glycogenesis %%% Lipolysis %%% Gluconeogenesis $$$
Q132
An investigator is studying heme biosynthesis in developing erythroid cells. After selective destruction of hemoglobin molecules, it is found that certain cells are unable to regenerate new heme molecules. A lack of which of the following structures would most likely explain this observation?
Q133
A 56-year-old man presents to his primary care doctor to discuss his plans for diet and exercise. He currently has hypertension treated with thiazide diuretics but is otherwise healthy. On exam, his temperature is 98.8°F (37.1°C), blood pressure is 122/84 mmHg, pulse is 70/min, and respirations are 12/min. His weight is 95.2 kilograms and his BMI is 31.0 kg/m^2. The patient is recommended to follow a 2000 kilocalorie diet with a 30:55 caloric ratio of fat to carbohydrates. Based on this patient’s body mass index and weight, he is recommended to consume 75 grams of protein per day. Which of the following represents the approximate number of grams of carbohydrates the patient should consume per day?
Q134
A 29-year-old female presents to the family physician concerned over the blue-black discoloration of her sclera and skin. She notes that at the end of her day, there are black stains in her underwear. The incomplete breakdown of which of the following amino acids is responsible for this presentation?
Q135
Two days after undergoing porcine aortic valve replacement surgery for aortic valve stenosis, a 62-year-old patient develops yellow discoloration of the sclera. His vital signs are within normal limits. Physical examination shows scleral icterus. Abdominal examination shows no abnormalities. Laboratory studies show:
Hematocrit 49%
Reticulocyte count 1.2%
Serum
AST 15 U/L
ALT 18 U/L
Bilirubin, total 2.8 mg/dL
Direct 0.3 mg/dL
Lactate dehydrogenase 62 U/L
Which of the following is the most likely underlying mechanism of this patient's laboratory findings?
Q136
A 21-year-old man presents to the emergency department with acute back pain. The pain began a few hours prior to presentation and is located on the left lower back. The pain is described to be “shock-like,” 9/10 in pain severity, and radiates to the left groin. His temperature is 98.6°F (37°C), blood pressure is 120/75 mmHg, pulse is 101/min, and respirations are 18/min. The patient appears uncomfortable and is mildly diaphoretic. There is costovertebral angle tenderness and genitourinary exam is unremarkable. A non-contrast computerized tomography (CT) scan of the abdomen and pelvis demonstrates an opaque lesion affecting the left ureter with mild hydronephrosis. Straining of the urine with urine crystal analysis is demonstrated. Which of the following amino acids is most likely poorly reabsorbed by this patient’s kidney?
Q137
A 66-year-old man weighing 50 kg (110 lb) is admitted to the hospital because of sepsis complicated by acute respiratory distress syndrome. The physician decides to initiate total parenteral nutrition and prescribes short-term hypocaloric intake of 20 kcal/kg/day with 20% of the total energy requirement provided by proteins and 30% provided by fats. The physician calculates that a total volume of 1100 mL/day should be infused during the parenteral nutrition therapy to maintain fluid balance. A colloid containing 10 g/dL of albumin and an emulsion with a fat concentration of 33 g/dL are used to prepare parenteral nutrition modules. Which of the following is the most appropriate module to meet the carbohydrate requirement in this patient over the next 24 hours?
Q138
A newborn undergoing the standard screening tests is found to have a positive test for reducing sugars. Further testing is performed and reveals that the patient does not have galactosemia, but rather is given a diagnosis of fructosuria. What levels of enzymatic activity are altered in this patient?
Q139
A 27-year-old man presents to the emergency department with painless yellowing of his skin. The patient states he is generally healthy and has no past medical history. He smokes 2 packs of cigarettes per day and was recently treated for a urinary tract infection with a single dose of ceftriaxone followed by a 7 day course of ciprofloxacin. He recently returned from a 3 day hiking trip and is an avid vegan. His only other medical history is a mild cough for the past few days. His temperature is 97.5°F (36.4°C), blood pressure is 122/82 mmHg, pulse is 85/min, respirations are 15/min, and oxygen saturation is 98% on room air. Physical exam reveals an abdomen which is non-tender. Mild scleral icterus and sublingual jaundice is noted. Which of the following is the most likely etiology of this patient’s symptoms?
Q140
An 8-year-old boy is referred to your office by his school for kyphoscoliosis. His mother recently noticed a change in the way he walks but thought it was a normal part of his growth. She notes that he has always been clumsy and has frequent falls. He has a history of type 1 diabetes mellitus for which he receives insulin. He has no other health problems and has been doing well in school. On physical exam his temperature is 99°F (37.2°C), blood pressure is 110/75 mmHg, pulse is 80/min, and respirations are 19/min. Cardiopulmonary exam is unremarkable. On neurologic exam you notice nystagmus. Patellar reflex is absent and the patient has a staggering gait. The disorder most likely responsible for this patient’s presentation is due to an abnormality in which of the following?
Metabolism US Medical PG Practice Questions and MCQs
Question 131: A 46-year-old man comes to the physician for a follow-up examination. He has type 2 diabetes mellitus and hypertension. Current medications include metformin and lisinopril. He reports that he has adhered to his diet and medication regimen. His hemoglobin A1c is 8.6%. Insulin glargine is added to his medication regimen. Which of the following sets of changes is most likely to occur in response to this new medication?
$$$ Glycolysis %%% Glycogenesis %%% Lipolysis %%% Gluconeogenesis $$$
A. ↓ ↓ ↑ ↑
B. ↑ ↓ ↑ ↓
C. ↓ ↑ ↓ ↑
D. ↑ ↑ ↓ ↓ (Correct Answer)
E. ↑ ↓ ↑ ↑
Explanation: ***↑ ↑ ↓ ↓***
- Insulin **increases glucose utilization** by promoting glycolysis and increases glucose storage by promoting glycogenesis.
- Insulin **inhibits glucose production** by decreasing lipolysis and gluconeogenesis.
*↓ ↓ ↑ ↑*
- This option incorrectly suggests that insulin would decrease glycolysis and glycogenesis, which are pathways for glucose utilization and storage.
- It also incorrectly suggests that insulin would increase lipolysis and gluconeogenesis, which are pathways for glucose production.
*↑ ↓ ↑ ↓*
- This option correctly indicates an increase in glycolysis and a decrease in gluconeogenesis, but incorrectly suggests a decrease in glycogenesis and an increase in lipolysis.
- Insulin's primary role is to lower blood glucose, which involves promoting both glucose utilization (glycolysis) and storage (glycogenesis).
*↓ ↑ ↓ ↑*
- This option incorrectly suggests a decrease in glycolysis and an increase in gluconeogenesis, which would lead to higher blood glucose.
- While it correctly shows an increase in glycogenesis and a decrease in lipolysis, the overall pattern does not match insulin's coordinated metabolic effects.
*↑ ↓ ↑ ↑*
- This option incorrectly suggests a decrease in glycogenesis and an increase in lipolysis and gluconeogenesis, which would lead to higher blood glucose.
- Insulin's main actions are to promote glucose uptake and storage and to inhibit glucose production.
Question 132: An investigator is studying heme biosynthesis in developing erythroid cells. After selective destruction of hemoglobin molecules, it is found that certain cells are unable to regenerate new heme molecules. A lack of which of the following structures would most likely explain this observation?
A. Nucleus
B. Peroxisomes
C. Smooth endoplasmic reticulum
D. Mitochondria (Correct Answer)
E. Golgi apparatus
Explanation: ***Mitochondria***
- Heme synthesis requires **mitochondria** for both the **initial** and **final steps** of the pathway.
- The first step, catalyzed by **ALA synthase** (δ-aminolevulinic acid synthase), occurs in the mitochondrial matrix.
- The final steps, including **coproporphyrinogen oxidase**, **protoporphyrinogen oxidase**, and critically, **ferrochelatase** (which inserts **iron** into **protoporphyrin IX**), all occur within the **mitochondria**.
- Without functional mitochondria, cells cannot initiate or complete heme synthesis, preventing the formation of new heme molecules.
*Nucleus*
- The nucleus contains the **genetic material** required to code for enzymes involved in heme synthesis, but it is not directly involved in the synthesis process itself.
- Mature **erythroid cells** (reticulocytes and erythrocytes) lose their nucleus but can still synthesize heme using existing mitochondria and cytosolic enzymes.
*Peroxisomes*
- Peroxisomes are involved in **fatty acid metabolism** (β-oxidation of very long chain fatty acids) and detoxification of reactive oxygen species; they play no direct role in heme synthesis.
- Their absence would not specifically impede heme regeneration.
*Smooth endoplasmic reticulum*
- The smooth endoplasmic reticulum is primarily involved in **lipid synthesis**, **detoxification**, and **steroid hormone production**.
- It does not contain the enzymes necessary for heme biosynthesis.
*Golgi apparatus*
- The Golgi apparatus is responsible for **modifying**, **sorting**, and **packaging proteins and lipids** for secretion or delivery to other organelles.
- It is not involved in the actual synthesis of heme precursors or the final assembly of the heme molecule.
Question 133: A 56-year-old man presents to his primary care doctor to discuss his plans for diet and exercise. He currently has hypertension treated with thiazide diuretics but is otherwise healthy. On exam, his temperature is 98.8°F (37.1°C), blood pressure is 122/84 mmHg, pulse is 70/min, and respirations are 12/min. His weight is 95.2 kilograms and his BMI is 31.0 kg/m^2. The patient is recommended to follow a 2000 kilocalorie diet with a 30:55 caloric ratio of fat to carbohydrates. Based on this patient’s body mass index and weight, he is recommended to consume 75 grams of protein per day. Which of the following represents the approximate number of grams of carbohydrates the patient should consume per day?
A. 67
B. 122
C. 275 (Correct Answer)
D. 232
E. 324
Explanation: ***275***
- The patient is recommended to follow a **2000 kilocalorie diet**. Given that the caloric ratio for carbohydrates is 55%, the calories from carbohydrates would be 0.55 * 2000 kcal = **1100 kcal**.
- Since **1 gram of carbohydrate provides approximately 4 kilocalories**, the total grams of carbohydrates would be 1100 kcal / 4 kcal/g = **275 grams**.
*67*
- This value is significantly lower than the calculated amount, likely arising from a miscalculation of the **percentage of carbohydrates** or the **caloric conversion factor**.
- A 67-gram carbohydrate intake from a 2000-kcal diet would mean only 268 kcal from carbohydrates, which is about 13.4% of the total calories, far less than the recommended 55%.
*122*
- This amount of carbohydrates would provide 488 kcal (122 g * 4 kcal/g), which is only about 24.4% of the total 2000 kcal diet.
- This value represents less than half of the recommended **55% caloric intake from carbohydrates**.
*232*
- This value corresponds to approximately 928 kcal from carbohydrates (232 g * 4 kcal/g).
- While closer, this is still lower than the 1100 kcal (55% of 2000 kcal) recommended for carbohydrates, indicating a miscalculation of the **percentage or total caloric intake**.
*324*
- This value corresponds to 1296 kcal from carbohydrates (324 g * 4 kcal/g).
- This amount would represent approximately 64.8% of the total 2000 kcal diet, which is higher than the recommended **55% caloric ratio for carbohydrates**.
Question 134: A 29-year-old female presents to the family physician concerned over the blue-black discoloration of her sclera and skin. She notes that at the end of her day, there are black stains in her underwear. The incomplete breakdown of which of the following amino acids is responsible for this presentation?
A. Leucine
B. Valine
C. Tyrosine (Correct Answer)
D. Methionine
E. Isoleucine
Explanation: ***Tyrosine***
- The symptoms described (blue-black **scleral and skin discoloration**, and dark urine staining underwear) are classic for **alkaptonuria**.
- Alkaptonuria results from a deficiency of **homogentisate oxidase**, an enzyme in the catabolic pathway of **tyrosine**, which leads to the accumulation of **homogentisic acid**.
*Leucine*
- Leucine is a **branched-chain amino acid**; disorders in its metabolism are typically associated with conditions like **Maple Syrup Urine Disease**.
- **Maple Syrup Urine Disease** presents with neurological symptoms, poor feeding, and a characteristic odor, not blue-black discoloration.
*Valine*
- Valine is another **branched-chain amino acid**, and its metabolic defects are also associated with conditions like **Maple Syrup Urine Disease**.
- Its accumulation does not lead to the specific pigmentary changes seen in alkaptonuria.
*Methionine*
- Methionine metabolism disorders include conditions such as **homocystinuria**.
- **Homocystinuria** is characterized by skeletal abnormalities, ocular problems, and intellectual disability, not blue-black discoloration.
*Isoleucine*
- Isoleucine is the third **branched-chain amino acid** and is also implicated in **Maple Syrup Urine Disease** when its metabolism is impaired.
- Clinical features of isoleucine metabolism defects do not include the blue-black pigmentation described.
Question 135: Two days after undergoing porcine aortic valve replacement surgery for aortic valve stenosis, a 62-year-old patient develops yellow discoloration of the sclera. His vital signs are within normal limits. Physical examination shows scleral icterus. Abdominal examination shows no abnormalities. Laboratory studies show:
Hematocrit 49%
Reticulocyte count 1.2%
Serum
AST 15 U/L
ALT 18 U/L
Bilirubin, total 2.8 mg/dL
Direct 0.3 mg/dL
Lactate dehydrogenase 62 U/L
Which of the following is the most likely underlying mechanism of this patient's laboratory findings?
A. Impaired bilirubin conjugation
B. Mechanical erythrocyte damage (Correct Answer)
C. Drug-induced toxicity
D. Absent hepatic glucuronosyltransferase
E. Impaired bilirubin excretion
Explanation: ***Mechanical erythrocyte damage***
- The patient's **porcine aortic valve replacement** can cause **hemolysis** due to high-velocity blood flow across the prosthetic valve, leading to fragmentation of red blood cells.
- This **hemolysis** releases **unconjugated bilirubin**, resulting in **jaundice** (scleral icterus) and elevated **total bilirubin** with low direct bilirubin (indirect hyperbilirubinemia).
- The presentation shows **predominantly indirect hyperbilirubinemia** (total 2.8 mg/dL with direct only 0.3 mg/dL), **normal liver enzymes**, which is consistent with hemolysis even with normal LDH in this early post-operative period.
*Impaired bilirubin conjugation*
- This condition would present with **unconjugated hyperbilirubinemia** but would not explain the specific context of recent prosthetic valve replacement.
- Examples include **Gilbert syndrome** or **Crigler-Najjar syndrome**, which are chronic conditions or genetic disorders, not acute post-surgical findings.
*Drug-induced toxicity*
- Drug-induced liver injury would typically manifest with elevated **liver enzymes (AST/ALT)**, which are normal in this patient.
- The timing (2 days post-surgery) and the specific findings (unconjugated hyperbilirubinemia with normal liver enzymes) are more consistent with **hemolysis** than drug toxicity.
*Absent hepatic glucuronosyltransferase*
- This refers to severe deficiency or absence of the enzyme required for **bilirubin conjugation**, as seen in **Crigler-Najjar syndrome Type I**.
- While it causes **unconjugated hyperbilirubinemia**, it does not explain the rapid onset following valve replacement; it is a congenital disorder that would have been evident earlier in life.
*Impaired bilirubin excretion*
- This would lead to **conjugated hyperbilirubinemia** (elevated direct bilirubin) and often elevated **liver enzymes** or **alkaline phosphatase**, indicating cholestasis or hepatic dysfunction.
- In this case, the **direct bilirubin is low (0.3 mg/dL)** and liver enzymes are normal, ruling out impaired excretion as the primary mechanism.
Question 136: A 21-year-old man presents to the emergency department with acute back pain. The pain began a few hours prior to presentation and is located on the left lower back. The pain is described to be “shock-like,” 9/10 in pain severity, and radiates to the left groin. His temperature is 98.6°F (37°C), blood pressure is 120/75 mmHg, pulse is 101/min, and respirations are 18/min. The patient appears uncomfortable and is mildly diaphoretic. There is costovertebral angle tenderness and genitourinary exam is unremarkable. A non-contrast computerized tomography (CT) scan of the abdomen and pelvis demonstrates an opaque lesion affecting the left ureter with mild hydronephrosis. Straining of the urine with urine crystal analysis is demonstrated. Which of the following amino acids is most likely poorly reabsorbed by this patient’s kidney?
A. Isoleucine
B. Aspartic acid
C. Phenylalanine
D. Lysine (Correct Answer)
E. Histidine
Explanation:
***Lysine***
- The patient's symptoms (acute, severe, radiating back pain, CVA tenderness, hydronephrosis, and opaque lesion on CT) are highly characteristic of a **kidney stone**.
- Given the patient's young age and the nature of the amino acid question, thinking of **cystinuria** is appropriate, where the basic amino acids **COLA** (cystine, ornithine, lysine, arginine) are poorly reabsorbed.
*Isoleucine*
- **Isoleucine** is a branched-chain amino acid, not one of the basic amino acids impacted by cystinuria.
- Its malabsorption is not associated with the formation of kidney stones.
*Aspartic acid*
- **Aspartic acid** is an acidic amino acid and is not involved in the transport defects seen in cystinuria.
- There is no direct link between aspartic acid malabsorption and kidney stone formation.
*Phenylalanine*
- **Phenylalanine** is an aromatic amino acid and its metabolism is associated with disorders like phenylketonuria, not kidney stones.
- It is not one of the amino acids whose renal reabsorption is impaired in cystinuria.
*Histidine*
- **Histidine** is an essential amino acid, but it is not one of the basic amino acids (COLA) whose transport is affected in cystinuria.
- Poor reabsorption of histidine is not typically associated with kidney stone formation.
Question 137: A 66-year-old man weighing 50 kg (110 lb) is admitted to the hospital because of sepsis complicated by acute respiratory distress syndrome. The physician decides to initiate total parenteral nutrition and prescribes short-term hypocaloric intake of 20 kcal/kg/day with 20% of the total energy requirement provided by proteins and 30% provided by fats. The physician calculates that a total volume of 1100 mL/day should be infused during the parenteral nutrition therapy to maintain fluid balance. A colloid containing 10 g/dL of albumin and an emulsion with a fat concentration of 33 g/dL are used to prepare parenteral nutrition modules. Which of the following is the most appropriate module to meet the carbohydrate requirement in this patient over the next 24 hours?
A. 500 mL of 25% dextrose solution (Correct Answer)
B. 750 mL of 25% dextrose solution
C. 750 mL of 10% dextrose solution
D. 500 mL of 10% dextrose solution
E. 250 mL of 50% dextrose solution
Explanation: ***500 mL of 25% dextrose solution***
- The patient requires 1000 kcal/day total (50 kg * 20 kcal/kg/day). With 20% from protein (200 kcal) and 30% from fat (300 kcal), 500 kcal must come from carbohydrates. Given that **1 g of dextrose provides 3.4 kcal**, 500 kcal requires approximately 147 g of dextrose (500 kcal / 3.4 kcal/g). A **25% dextrose solution contains 250 g of dextrose per liter**, so 500 mL would provide 125 g of dextrose (0.5 L * 250 g/L), which translates to 425 kcal (125 g * 3.4 kcal/g). This is the closest and most appropriate option.
- While not exactly 500 kcal, this option delivers the closest amount of carbohydrate calories while fitting within fluid restrictions and is a common concentration used in TPN.
*750 mL of 25% dextrose solution*
- This option would provide approximately 187.5 g of dextrose (0.75 L * 250 g/L), resulting in 637.5 kcal. This is **too high a carbohydrate load** for the patient's calculated needs (500 kcal from carbs) and would exceed the desired energy distribution.
- Additionally, this volume might lead to **fluid overload** given the 1100 mL/day total fluid restriction.
*750 mL of 10% dextrose solution*
- This option provides approximately 75 g of dextrose (0.75 L * 100 g/L), resulting in 255 kcal. This is **insufficient to meet the required 500 kcal** from carbohydrates.
- While the volume is high, the caloric content from carbohydrate is low.
*500 mL of 10% dextrose solution*
- This option provides approximately 50 g of dextrose (0.5 L * 100 g/L), resulting in 170 kcal. This is **significantly below the target of 500 kcal** from carbohydrates and would lead to underfeeding.
- It would also leave a substantial amount of the 1100mL fluid volume unaccounted for if this were the only carbohydrate source.
*250 mL of 50% dextrose solution*
- This option provides approximately 125 g of dextrose (0.25 L * 500 g/L), resulting in 425 kcal. While the caloric content is similar to the correct answer, using **50% dextrose in a standard TPN formulation can be challenging** due to its high osmolality, and typically requires central line administration, which might not be practical for a "module" if other components dilute it.
- A 25% solution is generally preferred for its better compatibility within TPN admixtures and safer peripheral administration if necessary.
Question 138: A newborn undergoing the standard screening tests is found to have a positive test for reducing sugars. Further testing is performed and reveals that the patient does not have galactosemia, but rather is given a diagnosis of fructosuria. What levels of enzymatic activity are altered in this patient?
A. Hexokinase decreased; fructokinase decreased
B. Hexokinase unchanged; fructokinase unchanged
C. Hexokinase increased; fructokinase increased
D. Hexokinase increased; fructokinase decreased
E. Hexokinase unchanged; fructokinase decreased (Correct Answer)
Explanation: ***Hexokinase unchanged; fructokinase decreased***
- **Essential fructosuria** is caused by a deficiency in **fructokinase**, the enzyme responsible for the first step of fructose metabolism (fructose → fructose-1-phosphate).
- This results in **decreased or absent fructokinase activity**, leading to fructose accumulation in blood and urine (positive reducing sugar test).
- **Hexokinase activity remains unchanged** - there is no upregulation or compensatory increase in hexokinase. The enzyme maintains its normal baseline activity.
- Essential fructosuria is a **benign, asymptomatic condition** with no metabolic stress, so no compensatory enzyme changes occur.
- The small amount of fructose that needs metabolism can be handled by normal baseline hexokinase activity (hexokinase has broad substrate specificity).
*Hexokinase decreased; fructokinase decreased*
- While **fructokinase is decreased** in essential fructosuria, hexokinase activity is not decreased.
- Hexokinase is a constitutively expressed glycolytic enzyme whose activity does not change in this benign condition.
*Hexokinase unchanged; fructokinase unchanged*
- This is incorrect because **fructokinase activity is specifically decreased** in essential fructosuria, which is the defining enzymatic defect of the condition.
- The decreased fructokinase activity causes fructose to accumulate and appear in the urine.
*Hexokinase increased; fructokinase increased*
- **Fructokinase is decreased, not increased** - an increase would prevent the fructose accumulation characteristic of this condition.
- Hexokinase activity does not increase as essential fructosuria causes no metabolic stress requiring compensation.
*Hexokinase increased; fructokinase decreased*
- While **fructokinase is decreased** in essential fructosuria, hexokinase activity does not increase.
- This is a benign condition with no compensatory enzyme upregulation - hexokinase maintains normal baseline activity levels.
Question 139: A 27-year-old man presents to the emergency department with painless yellowing of his skin. The patient states he is generally healthy and has no past medical history. He smokes 2 packs of cigarettes per day and was recently treated for a urinary tract infection with a single dose of ceftriaxone followed by a 7 day course of ciprofloxacin. He recently returned from a 3 day hiking trip and is an avid vegan. His only other medical history is a mild cough for the past few days. His temperature is 97.5°F (36.4°C), blood pressure is 122/82 mmHg, pulse is 85/min, respirations are 15/min, and oxygen saturation is 98% on room air. Physical exam reveals an abdomen which is non-tender. Mild scleral icterus and sublingual jaundice is noted. Which of the following is the most likely etiology of this patient’s symptoms?
A. Ceftriaxone administration
B. Carotenoid consumption
C. Pancreatic cancer
D. Gilbert syndrome (Correct Answer)
E. Crigler-Najjar syndrome
Explanation: ***Gilbert syndrome***
- The patient presents with **painless jaundice** and **scleral icterus** but is otherwise healthy, which is typical for Gilbert syndrome. Stressors like a recent **hiking trip** or mild illness can precipitate episodes of visible jaundice in individuals with this condition.
- Gilbert syndrome is a common, benign, inherited disorder characterized by intermittent episodes of **unconjugated hyperbilirubinemia** due to reduced activity of the hepatic enzyme **UDP-glucuronosyltransferase (UGT1A1)**.
*Ceftriaxone administration*
- While ceftriaxone can rarely cause biliary sludge or cholelithiasis, leading to obstructive jaundice, the patient's symptoms are mild and **painless**, and ceftriaxone typically causes an **elevated direct bilirubin**, not unconjugated hyperbilirubinemia.
- The patient's presentation with mild, intermittent jaundice is not characteristic of significant **biliary obstruction** that would be related to ceftriaxone.
*Carotenoid consumption*
- Excessive consumption of **carotenoids** can cause **carotenemia**, leading to yellowing of the skin, especially on the palms and soles, but it **does not cause scleral icterus** or sublingual jaundice.
- The patient's **vegan diet** might suggest high carotenoid intake, but the presence of scleral icterus rules out carotenemia as the primary cause of the generalized yellowing.
*Pancreatic cancer*
- Pancreatic cancer in a 27-year-old is extremely rare and typically presents with **obstructive jaundice** (elevated direct bilirubin), often accompanied by other symptoms such as **weight loss**, **abdominal pain**, or **dark urine**.
- The patient's good general health, normal vitals, and lack of other systemic symptoms make pancreatic cancer highly unlikely.
*Crigler-Najjar syndrome*
- Crigler-Najjar syndrome is a rare, severe genetic disorder causing **severe unconjugated hyperbilirubinemia** due to near-total absence (Type I) or significantly reduced (Type II) **UGT1A1 activity**.
- Type I typically presents in **neonates** with severe jaundice and **kernicterus**, while Type II presents later but is generally more symptomatic and persistent than what is described in this patient, who has mild, intermittent jaundice.
Question 140: An 8-year-old boy is referred to your office by his school for kyphoscoliosis. His mother recently noticed a change in the way he walks but thought it was a normal part of his growth. She notes that he has always been clumsy and has frequent falls. He has a history of type 1 diabetes mellitus for which he receives insulin. He has no other health problems and has been doing well in school. On physical exam his temperature is 99°F (37.2°C), blood pressure is 110/75 mmHg, pulse is 80/min, and respirations are 19/min. Cardiopulmonary exam is unremarkable. On neurologic exam you notice nystagmus. Patellar reflex is absent and the patient has a staggering gait. The disorder most likely responsible for this patient’s presentation is due to an abnormality in which of the following?
A. Myophosphorylase
B. Myotonin protein kinase
C. Fructokinase
D. Frataxin (Correct Answer)
E. Fibrillin
Explanation: ***Frataxin***
- This patient's presentation with **kyphoscoliosis**, **gait abnormalities (staggering gait)**, **ataxia (clumsiness, falls)**, **nystagmus**, **absent patellar reflexes**, and **type 1 diabetes mellitus** is highly suggestive of **Friedreich ataxia**.
- **Friedreich ataxia** is an autosomal recessive neurodegenerative disorder caused by a **GAA trinucleotide repeat expansion** in the *FXN* gene, which codes for the mitochondrial protein **frataxin**.
*Myophosphorylase*
- An abnormality in **myophosphorylase** (McArdle disease) typically presents with **exercise-induced muscle pain, cramps, and myoglobinuria**, not the progressive neurological and systemic features seen in this patient.
- Patients with **McArdle disease** usually have normal neurological exams outside of muscle symptoms, and **diabetes mellitus** is not a characteristic feature.
*Myotonin protein kinase*
- Defects in **myotonin protein kinase** are associated with **myotonic dystrophy**, which is characterized by **myotonia** (delayed muscle relaxation), **muscle weakness**, and often **cataracts, frontal baldness, and testicular atrophy**.
- While type 1 diabetes can be associated with myotonic dystrophy, the combination of **kyphoscoliosis, nystagmus, ataxia, and absent reflexes** is not typical.
*Fructokinase*
- An abnormality in **fructokinase** leads to **essential fructosuria**, a benign metabolic disorder where fructose is not metabolized and is excreted in the urine.
- It is an **asymptomatic condition** and does not cause neurological deficits, kyphoscoliosis, or gait disturbances.
*Fibrillin*
- Defects in **fibrillin** (specifically fibrillin-1) are responsible for **Marfan syndrome**, a connective tissue disorder.
- **Marfan syndrome** is characterized by **tall stature, long limbs and digits (arachnodactyly), joint hypermobility, cardiovascular abnormalities (aortic root dilation), and ocular problems (lens ectopia)**, which do not align with the neurological and systemic symptoms of this patient.
