Myeloperoxidase (MPO) is a heme-containing molecule that is found in the azurophilic granules of neutrophils. Upon release, the enzyme catalyzes hypochlorous acid production during the phagocytic response. In the setting of pneumonia, which of the following clinical findings is most directly associated with myeloperoxidase activity?
Q152
A 24-year-old man is running a marathon. Upon reaching the finish line, his serum lactate levels were measured and were significantly increased as compared to his baseline. Which of the following pathways converts the lactate produced by muscles into glucose and transports it back to the muscles?
Q153
A 33-year-old man presents with yellowing of the eyes. He says symptoms onset acutely 3 days ago and have not improved. He says he has had similar episodes for the past 10 years. Each episode is self-limited, lasting no more than 3–5 days. The patient denies any recent history of nausea, weight loss, abdominal pain, light-colored stools, dark urine, or pruritus. Current medications are herbal supplements and a multivitamin. The patient is afebrile and vital signs are within normal limits. His BMI is 32 kg/m2. Physical exam is unremarkable. Laboratory findings are significant for the following:
Total bilirubin 3 mg/dL
Direct bilirubin 0.2 mg/dL
AST/ALT/Alkaline phosphatase Normal
Hematocrit/lactate dehydrogenase (LDH)/haptoglobin Normal
Which of the following is the most likely diagnosis in this patient?
Q154
A 2-month-old boy is brought to the emergency department 25 minutes after having a seizure. He has had multiple seizures during the past week. His mother has noticed that he has become lethargic and has had a weak cry for the past month. He was born at 37 weeks' gestation. He is at the 20th percentile for height and 15th percentile for weight. His temperature is 36.7°C (98°F), respirations are 50/min, and pulse is 140/min. Examination shows a soft and nontender abdomen. The liver is palpated 4 cm below the right costal margin; there is no splenomegaly. Serum studies show:
Na+ 137 mEq/L
Cl- 103 mEq/L
K+ 3.9 mEq/L
Glucose 32 mg/dL
Calcium 9.6 mg/dL
Total cholesterol 202 mg/dL
Triglycerides 260 mg/dL
Lactate 4.2 mEq/L (N = 0.5 - 2.2 mEq/L)
A deficiency of which of the following enzymes is the most likely cause of this infant's symptoms?
Q155
A 3-week-old male is brought to the emergency department because of increasing lethargy. He was born at home without prenatal care or neonatal screening and appeared to be normal at birth. Despite this, his parents noticed that he would vomit after breastfeeding. He then progressively became more lethargic and began to have a few episodes of diarrhea after feeding. His parents do not recall any significant family history and neither of his siblings have had similar symptoms. Upon presentation, the infant is found to be generally unresponsive with mild hepatomegaly. Physical exam further reveals signs of clouding in the lenses of his eyes bilaterally. The levels of which of the following metabolites will be most dramatically elevated in this patient?
Q156
A 12-year-old girl is brought to the physician by her mother 2 hours after cutting her hand while playing in the yard. Examination of the right hand shows a 2-cm laceration on the thenar region of the palm with some surrounding tenderness and erythema. The right palm appears mildly swollen in comparison to the left. In response to this patient's injury, the endothelial cells lining the blood vessels of the affected area express increased numbers of cellular adhesion molecules. Which of the following mediators is most likely directly responsible for the described change?
Q157
A researcher discovers a new inhibitor for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that she believes will be more effective than current drugs. The compound she discovers uses the same mechanism of inhibiting the target enzyme as current drugs of this class; however, it has fewer off target effects and side effects. Therefore, she thinks that this drug can be used at higher concentrations. In order to study the effects of this compound on the enzyme, she conducts enzyme kinetics studies. Specifically, she plots the substrate concentration of the enzyme on the x-axis and its initial reaction velocity on the y-axis. She then calculates the Michaelis-Menten constant (Km) as well as the maximum reaction velocity (Vmax) of the enzyme. Compared to values when studying the enzyme alone, what will be the values seen after the inhibitor is added?
Q158
An investigator is studying a hereditary defect in the mitochondrial enzyme succinyl-CoA synthetase. In addition to succinate, the reaction catalyzed by this enzyme produces a molecule that is utilized as an energy source for protein translation. This molecule is also required for which of the following conversion reactions?
Q159
A 30-year-old African American G1P0 mother gives birth to a male infant at 33 weeks' gestation. The mother had no prenatal care and took no prenatal vitamins. The child’s postnatal period was complicated by neonatal sepsis due to group B Streptococcus. He required a two week stay in the neonatal intensive care unit to receive antibiotics, cardiopulmonary support, and intravenous nutrition. He eventually recovered and was discharged. At a normal follow-up visit to the pediatrician’s office one month later, the mother asks about the child’s skin color and hair color. On examination, the child has white hair and diffusely pale skin. The child’s irises appear translucent. Further questioning of the mother reveals that there is a distant family history of blindness. This child most likely has a defect in an enzyme involved in the metabolism of which of the following molecules?
Q160
An otherwise healthy 45-year-old woman comes to the physician because of a 1-year history of episodic abdominal cramps, bloating, and flatulence. The symptoms worsen when she consumes pizza or ice cream and have become more frequent over the past 4 months. Lactose intolerance is suspected. Which of the following would most strongly support the diagnosis of lactose intolerance?
Metabolism US Medical PG Practice Questions and MCQs
Question 151: Myeloperoxidase (MPO) is a heme-containing molecule that is found in the azurophilic granules of neutrophils. Upon release, the enzyme catalyzes hypochlorous acid production during the phagocytic response. In the setting of pneumonia, which of the following clinical findings is most directly associated with myeloperoxidase activity?
A. Shortness of breath
B. Green color of sputum (Correct Answer)
C. Rust-tinged sputum
D. Cough
E. Fever
Explanation: ***Green color of sputum***
- Myeloperoxidase contributes to the **greenish color of sputum** due to its heme content and enzymatic activity, which involves the formation of a green pigment during the oxidation of chloride ions.
- In pneumonia, activated neutrophils release myeloperoxidase as part of the immune response, leading to the characteristic **greenish discoloration** often observed in a patient's sputum.
*Shortness of breath*
- Shortness of breath, or **dyspnea**, is a common symptom of pneumonia reflecting impaired gas exchange and increased work of breathing.
- It is a **physiological response** to lung inflammation and consolidation, not a direct end result of myeloperoxidase activity.
*Rust-tinged sputum*
- **Rust-tinged sputum** is classically associated with **Streptococcus pneumoniae** pneumonia and is due to the breakdown of red blood cells and the presence of hemoglobin metabolites.
- While it indicates an infection, it is not directly linked to the enzymatic action or color of myeloperoxidase itself.
*Cough*
- **Cough** is a vital **protective reflex** in pneumonia, aiming to clear respiratory secretions and foreign material from the airways.
- It is a symptom of airway irritation and inflammation, rather than a direct visual outcome of biochemical reactions involving myeloperoxidase.
*Fever*
- **Fever** is a systemic manifestation of the body's generalized **inflammatory response** to infection, mediated by pyrogens.
- It is a non-specific symptom indicating an active infection, not a direct consequence of myeloperoxidase activity or its visual manifestation.
Question 152: A 24-year-old man is running a marathon. Upon reaching the finish line, his serum lactate levels were measured and were significantly increased as compared to his baseline. Which of the following pathways converts the lactate produced by muscles into glucose and transports it back to the muscles?
A. Citric acid cycle
B. Glycolysis
C. Glycogenesis
D. Pentose phosphate pathway
E. Cori cycle (Correct Answer)
Explanation: ***Cori cycle***
- The **Cori cycle** is the metabolic pathway that converts **lactate** produced by anaerobic glycolysis in muscles (especially during intense exercise) back to **glucose in the liver** via gluconeogenesis.
- During strenuous exercise, muscles rely on anaerobic glycolysis when oxygen supply is insufficient, producing lactate and 2 ATP per glucose.
- The lactate is transported via bloodstream to the liver, where it is converted back to glucose (requiring 6 ATP), which then returns to muscles for energy or glycogen storage.
- This cycle allows muscles to continue generating ATP anaerobically while the liver handles lactate clearance.
*Citric acid cycle*
- The **citric acid cycle** (Krebs cycle) oxidizes **acetyl-CoA** to generate ATP, NADH, and FADH₂ in the mitochondrial matrix under aerobic conditions.
- It does not convert lactate to glucose; rather, pyruvate can be converted to acetyl-CoA to enter this cycle for complete oxidation.
- This is an aerobic process and does not involve the liver-muscle lactate-glucose exchange.
*Glycolysis*
- **Glycolysis** is the metabolic pathway that breaks down **glucose into pyruvate**, generating 2 ATP and 2 NADH per glucose molecule.
- Under anaerobic conditions, pyruvate is converted to lactate to regenerate NAD⁺ for continued glycolysis.
- This is the opposite of what the question asks—glycolysis produces lactate from glucose, not glucose from lactate.
*Glycogenesis*
- **Glycogenesis** is the process of synthesizing **glycogen from glucose** for storage, primarily in liver and muscle tissue.
- While it involves glucose storage, it does not convert lactate back to glucose or involve the metabolic exchange between muscles and liver described in the question.
*Pentose phosphate pathway*
- The **pentose phosphate pathway** (hexose monophosphate shunt) produces **NADPH** for reductive biosynthesis and **ribose-5-phosphate** for nucleotide synthesis.
- It branches from glycolysis but is not involved in lactate metabolism or the muscle-liver glucose-lactate exchange.
Question 153: A 33-year-old man presents with yellowing of the eyes. He says symptoms onset acutely 3 days ago and have not improved. He says he has had similar episodes for the past 10 years. Each episode is self-limited, lasting no more than 3–5 days. The patient denies any recent history of nausea, weight loss, abdominal pain, light-colored stools, dark urine, or pruritus. Current medications are herbal supplements and a multivitamin. The patient is afebrile and vital signs are within normal limits. His BMI is 32 kg/m2. Physical exam is unremarkable. Laboratory findings are significant for the following:
Total bilirubin 3 mg/dL
Direct bilirubin 0.2 mg/dL
AST/ALT/Alkaline phosphatase Normal
Hematocrit/lactate dehydrogenase (LDH)/haptoglobin Normal
Which of the following is the most likely diagnosis in this patient?
A. Cholelithiasis
B. Gilbert’s syndrome (Correct Answer)
C. Medication-induced hemolysis
D. Crigler-Najjar syndrome type 1
E. Dubin-Johnson syndrome
Explanation: ***Gilbert’s syndrome***
- The patient's history of **recurrent, self-limited episodes of jaundice** (yellowing of the eyes) with normal liver enzymes and a predominance of **unconjugated (indirect) bilirubin** (3 mg/dL total, 0.2 mg/dL direct) is characteristic of Gilbert's syndrome.
- This benign genetic condition is caused by a partial deficiency of **UGT1A1 enzyme**, leading to impaired bilirubin conjugation, especially during stress, fasting, or illness.
*Cholelithiasis*
- **Cholelithiasis** typically presents with biliary colic or complications like **obstructive jaundice**, characterized by elevated direct bilirubin, alkaline phosphatase, and often abdominal pain, which are absent here.
- The absence of dark urine, light-colored stools, and pruritus further argues against biliary obstruction.
*Medication-induced hemolysis*
- **Hemolysis** would lead to elevated indirect bilirubin, but also an increase in **LDH** and a decrease in **haptoglobin**, along with anemia, none of which are present in this patient.
- The patient denies current medications that are known to cause hemolysis (only herbal supplements and multivitamins).
*Crigler-Najjar syndrome type 1*
- **Crigler-Najjar syndrome type 1** is a much more severe condition with a complete absence of UGT1A1 activity, resulting in **profoundly elevated indirect bilirubin** (often >20 mg/dL) and neurological complications (kernicterus) typically manifesting in infancy.
- The patient's milder, intermittent symptoms and normal neurological status rule out this diagnosis.
*Dubin-Johnson syndrome*
- **Dubin-Johnson syndrome** is characterized by **impaired excretion of conjugated (direct) bilirubin** into the bile, leading to predominantly elevated direct bilirubin and dark urine, which are not seen in this patient.
- The liver may appear dark on biopsy due to impaired excretion of epinephrine metabolites.
Question 154: A 2-month-old boy is brought to the emergency department 25 minutes after having a seizure. He has had multiple seizures during the past week. His mother has noticed that he has become lethargic and has had a weak cry for the past month. He was born at 37 weeks' gestation. He is at the 20th percentile for height and 15th percentile for weight. His temperature is 36.7°C (98°F), respirations are 50/min, and pulse is 140/min. Examination shows a soft and nontender abdomen. The liver is palpated 4 cm below the right costal margin; there is no splenomegaly. Serum studies show:
Na+ 137 mEq/L
Cl- 103 mEq/L
K+ 3.9 mEq/L
Glucose 32 mg/dL
Calcium 9.6 mg/dL
Total cholesterol 202 mg/dL
Triglycerides 260 mg/dL
Lactate 4.2 mEq/L (N = 0.5 - 2.2 mEq/L)
A deficiency of which of the following enzymes is the most likely cause of this infant's symptoms?
A. Galactose 1-phosphate uridyltransferase
B. Glycogen branching enzyme
C. Glucose 6-phosphatase (Correct Answer)
D. Fructokinase
E. Acid maltase
Explanation: ***Glucose 6-phosphatase***
- The constellation of **hypoglycemia**, **lactic acidosis**, **hepatomegaly**, and **hyperlipidemia** in an infant is characteristic of **Type I glycogen storage disease (von Gierke's disease)**, which is caused by a deficiency of glucose 6-phosphatase.
- Seizures and lethargy are common manifestations of severe hypoglycemia in infants.
*Galactose 1-phosphate uridyltransferase*
- Deficiency of this enzyme causes **classic galactosemia**, which typically presents with **jaundice**, **cataracts**, **vomiting**, and **failure to thrive**, usually after initiation of milk feeds.
- While patients can develop hepatomegaly and hypoglycemia, the prominent lactic acidosis and hyperlipidemia seen here are less typical.
*Glycogen branching enzyme*
- Deficiency causes **Type IV glycogen storage disease (Andersen's disease)**, characterized by **hepatosplenomegaly**, **failure to thrive**, and progressive cirrhosis.
- Hypoglycemia is generally less severe, and lactic acidosis and hyperlipidemia are not primary features in the same way as Type I GSD.
*Fructokinase*
- Deficiency causes **essential fructosuria**, a benign condition where fructose accumulates in the urine.
- It is typically asymptomatic and does not lead to hypoglycemia, lactic acidosis, or hepatomegaly.
*Acid maltase*
- Deficiency (alpha-1,4-glucosidase) causes **Type II glycogen storage disease (Pompe's disease)**, which primarily affects skeletal and cardiac muscle.
- The infantile form presents with **severe hypotonia** ("floppy baby"), **cardiomyopathy**, and **macroglossia**. Hepatomegaly, hypoglycemia, and lactic acidosis are not prominent features.
Question 155: A 3-week-old male is brought to the emergency department because of increasing lethargy. He was born at home without prenatal care or neonatal screening and appeared to be normal at birth. Despite this, his parents noticed that he would vomit after breastfeeding. He then progressively became more lethargic and began to have a few episodes of diarrhea after feeding. His parents do not recall any significant family history and neither of his siblings have had similar symptoms. Upon presentation, the infant is found to be generally unresponsive with mild hepatomegaly. Physical exam further reveals signs of clouding in the lenses of his eyes bilaterally. The levels of which of the following metabolites will be most dramatically elevated in this patient?
A. Fructose
B. Lactose
C. Galactose
D. Galactose-1-phosphate (Correct Answer)
E. Fructose-1-phosphate
Explanation: ***Galactose-1-phosphate***
- This patient's presentation with **vomiting after breastfeeding**, progressive **lethargy**, hepatomegaly, and **bilateral cataracts** is highly suggestive of **classic galactosemia**. This autosomal recessive disorder results from a deficiency in **galactose-1-phosphate uridylyltransferase (GALT)**.
- The deficiency of GALT leads to an accumulation of **galactose-1-phosphate** in various tissues, causing toxicity to the liver, brain, and eyes.
*Fructose*
- **Fructose intolerance** (hereditary fructose intolerance) is caused by a deficiency of **aldolase B**, leading to the accumulation of **fructose-1-phosphate**.
- While it can cause similar symptoms like vomiting, lethargy, and hepatomegaly, it is typically triggered by **fructose ingestion** (fruits, sucrose), which is not the primary carbohydrate source for a 3-week-old exclusively fed breast milk (containing lactose).
*Lactose*
- **Lactose intolerance** is due to a deficiency of lactase, leading to the malabsorption of lactose.
- Symptoms are primarily gastrointestinal, including **diarrhea, bloating, and abdominal pain**, but do not typically involve severe lethargy, hepatomegaly, or cataracts. The unmetabolized lactose itself does not accumulate to toxic levels.
*Galactose*
- While galactose is the substrate for the deficient enzyme in galactosemia, the most dramatically elevated and toxic metabolite is **galactose-1-phosphate**, not free galactose.
- Galactose is converted to galactose-1-phosphate before the metabolic block occurs.
*Fructose-1-phosphate*
- As mentioned, this metabolite accumulates in **hereditary fructose intolerance**, not galactosemia.
- The combination of breastfeeding and cataracts points strongly to a disorder of galactose metabolism rather than fructose metabolism.
Question 156: A 12-year-old girl is brought to the physician by her mother 2 hours after cutting her hand while playing in the yard. Examination of the right hand shows a 2-cm laceration on the thenar region of the palm with some surrounding tenderness and erythema. The right palm appears mildly swollen in comparison to the left. In response to this patient's injury, the endothelial cells lining the blood vessels of the affected area express increased numbers of cellular adhesion molecules. Which of the following mediators is most likely directly responsible for the described change?
A. Interferon alpha
B. Interleukin-10
C. Interleukin-1 (Correct Answer)
D. Interferon gamma
E. Interleukin-6
Explanation: ***Interleukin-1***
- **IL-1** is a potent **pro-inflammatory cytokine** that directly induces the expression of **cellular adhesion molecules** (CAMs) on endothelial cells.
- This action facilitates the **recruitment of leukocytes** to the site of injury, a crucial step in the inflammatory response observed with pain, tenderness, and swelling.
*Interferon alpha*
- **Interferon alpha (IFN-α)** is primarily an **antiviral cytokine** and has limited direct effects on the immediate upregulation of endothelial adhesion molecules in acute injury.
- It is more involved in the early immune response to viral infections by inhibiting viral replication and activating natural killer (NK) cells.
*Interleukin-10*
- **Interleukin-10 (IL-10)** is an **anti-inflammatory cytokine** that functions to suppress the immune response and downregulate the production of pro-inflammatory cytokines and adhesion molecules.
- Its role is to resolve inflammation, not to initiate or enhance the early stages of leukocyte recruitment in acute injury.
*Interferon gamma*
- **Interferon gamma (IFN-γ)** is a powerful **pro-inflammatory cytokine**, but its main role in inflammation is different from directly inducing immediate CAM expression.
- It **activates macrophages** and enhances antigen presentation, playing a more significant role in chronic inflammation and adaptive immunity rather than the initial endothelial activation in acute injury.
*Interleukin-6*
- **Interleukin-6 (IL-6)** is a major **pro-inflammatory cytokine**, but its primary function in acute inflammation is more related to the **acute phase response** (e.g., fever, CRP production) rather than direct and immediate upregulation of endothelial adhesion molecules.
- While it contributes to systemic inflammation, **IL-1** and **TNF-α** are more directly and immediately responsible for inducing CAM expression on endothelial cells.
Question 157: A researcher discovers a new inhibitor for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that she believes will be more effective than current drugs. The compound she discovers uses the same mechanism of inhibiting the target enzyme as current drugs of this class; however, it has fewer off target effects and side effects. Therefore, she thinks that this drug can be used at higher concentrations. In order to study the effects of this compound on the enzyme, she conducts enzyme kinetics studies. Specifically, she plots the substrate concentration of the enzyme on the x-axis and its initial reaction velocity on the y-axis. She then calculates the Michaelis-Menten constant (Km) as well as the maximum reaction velocity (Vmax) of the enzyme. Compared to values when studying the enzyme alone, what will be the values seen after the inhibitor is added?
A. Higher Km and same Vmax (Correct Answer)
B. Same Km and higher Vmax
C. Higher Km and lower Vmax
D. Same Km and lower Vmax
E. Same Km and same Vmax
Explanation: **_Higher Km and same Vmax_**
- The drug is an analog of the **substrate** and binds to the active site, thereby preventing the substrate from binding. This means that the substrate will compete with the inhibitor for binding, increasing the effective **Km**.
- Since the inhibitor is **reversible**, if enough substrate is added, the enzyme can still reach its normal **Vmax**.
*Same Km and higher Vmax*
- This option implies a more efficient enzyme or a larger quantity of enzyme, neither of which is the effect of a competitive inhibitor.
- A higher Vmax would suggest the inhibitor somehow enhances enzyme activity, which goes against the definition of an enzyme inhibitor.
*Higher Km and lower Vmax*
- This describes **mixed inhibition** where the inhibitor can bind to both the free enzyme and the enzyme-substrate complex, or a **non-competitive inhibitor** that binds to an allosteric site to reduce the catalytic efficiency, which is not the mechanism described.
- The problem states the inhibitor uses the same mechanism of inhibiting the target enzyme as current drugs of this class, which are typically competitive inhibitors for HMG-CoA reductase.
*Same Km and lower Vmax*
- This typically describes **non-competitive inhibition**, where the inhibitor binds to an allosteric site on the enzyme, altering its conformation and reducing its catalytic efficiency without affecting substrate binding affinity.
- In non-competitive inhibition, the Vmax is lowered because the enzyme's turnover rate is reduced, but the Km remains unchanged since the inhibitor does not affect substrate binding.
*Same Km and same Vmax*
- This would indicate that the inhibitor has **no effect** on the enzyme kinetics in terms of Km or Vmax, which contradicts the premise of discovering an effective inhibitor.
- An enzyme with competitive inhibition will always show a change in Km, or Vmax, or both.
Question 158: An investigator is studying a hereditary defect in the mitochondrial enzyme succinyl-CoA synthetase. In addition to succinate, the reaction catalyzed by this enzyme produces a molecule that is utilized as an energy source for protein translation. This molecule is also required for which of the following conversion reactions?
A. Oxaloacetate to phosphoenolpyruvate (Correct Answer)
B. Pyruvate to acetyl-CoA
C. Acetaldehyde to acetate
D. Glucose-6-phosphate to 6-phosphogluconolactone
E. Fructose-6-phosphate to fructose-1,6-bisphosphate
Explanation: ***Oxaloacetate to phosphoenolpyruvate***
- The reaction catalyzed by **succinyl-CoA synthetase** (also known as succinate thiokinase) produces **GTP** (guanosine triphosphate) from GDP and Pi, in addition to succinate.
- **GTP** is required for the conversion of **oxaloacetate** to **phosphoenolpyruvate** in gluconeogenesis, catalyzed by **PEP carboxykinase**.
*Pyruvate to acetyl-CoA*
- This reaction is catalyzed by the **pyruvate dehydrogenase complex** and produces NADH, not GTP.
- It is an irreversible step linking glycolysis to the citric acid cycle.
*Acetaldehyde to acetate*
- This reaction is catalyzed by **aldehyde dehydrogenase** and uses **NAD+** as a cofactor, producing NADH.
- It is involved in alcohol metabolism.
*Glucose-6-phosphate to 6-phosphogluconolactone*
- This is the first committed step of the **pentose phosphate pathway**, catalyzed by **glucose-6-phosphate dehydrogenase**.
- It uses **NADP+** as a cofactor, producing NADPH.
*Fructose-6-phosphate to fructose-1,6-bisphosphate*
- This reaction is a key regulatory step in **glycolysis**, catalyzed by **phosphofructokinase-1 (PFK-1)**.
- It consumes **ATP**, rather than producing GTP or utilizing it as a cofactor in the context of this question.
Question 159: A 30-year-old African American G1P0 mother gives birth to a male infant at 33 weeks' gestation. The mother had no prenatal care and took no prenatal vitamins. The child’s postnatal period was complicated by neonatal sepsis due to group B Streptococcus. He required a two week stay in the neonatal intensive care unit to receive antibiotics, cardiopulmonary support, and intravenous nutrition. He eventually recovered and was discharged. At a normal follow-up visit to the pediatrician’s office one month later, the mother asks about the child’s skin color and hair color. On examination, the child has white hair and diffusely pale skin. The child’s irises appear translucent. Further questioning of the mother reveals that there is a distant family history of blindness. This child most likely has a defect in an enzyme involved in the metabolism of which of the following molecules?
A. Leucine
B. Homocysteine
C. Phenylalanine
D. Homogentisic acid
E. DOPA (Correct Answer)
Explanation: ***DOPA***
- The symptoms of **white hair**, **pale skin**, and **translucent irises**, along with a family history of **blindness**, are classic signs of **oculocutaneous albinism**.
- **Oculocutaneous albinism** results from a defect in **tyrosinase**, an enzyme responsible for converting **DOPA** (3,4-dihydroxyphenylalanine) into **melanin**.
*Leucine*
- Defects in **leucine** metabolism are associated with **Maple Syrup Urine Disease**, characterized by sweet-smelling urine and neurological complications, not albinism.
- This condition involves impaired **branched-chain alpha-keto acid dehydrogenase** complex activity, leading to an accumulation of branched-chain amino acids.
*Homocysteine*
- Problems with **homocysteine** metabolism are seen in conditions like **homocystinuria**, which can cause developmental delay, skeletal abnormalities, and vascular issues, but not hypopigmentation.
- This is often due to deficiencies in **cystathionine beta-synthase** or other enzymes involved in folate and vitamin B12 metabolism.
*Phenylalanine*
- A defect in **phenylalanine** metabolism, specifically **phenylalanine hydroxylase**, leads to **phenylketonuria (PKU)**, which causes intellectual disability, seizures, and a musty odor, but not the specific ocular and cutaneous features described for albinism.
- While PKU can cause milder hypopigmentation due to reduced tyrosine availability, the described translucent irises and severe white hair are more indicative of albinism.
*Homogentisic acid*
- A defect in **homogentisic acid** metabolism causes **alkaptonuria**, characterized by dark urine upon standing, blue-black discoloration of cartilage (ochronosis), and early-onset arthritis, which are not present in this case.
- This condition results from a deficiency of **homogentisate 1,2-dioxygenase**.
Question 160: An otherwise healthy 45-year-old woman comes to the physician because of a 1-year history of episodic abdominal cramps, bloating, and flatulence. The symptoms worsen when she consumes pizza or ice cream and have become more frequent over the past 4 months. Lactose intolerance is suspected. Which of the following would most strongly support the diagnosis of lactose intolerance?
A. Normal small bowel histology
B. Positive lactose breath test with elevated hydrogen levels (Correct Answer)
C. Symptom improvement on lactose-free diet
D. Decreased lactase enzyme levels in duodenal biopsy
E. Osmotic diarrhea with stool pH < 5.5
Explanation: ***Positive lactose breath test with elevated hydrogen levels***
- A **lactose breath test** measures hydrogen in the breath, which is produced by colonic bacteria fermenting undigested lactose. Elevated levels confirm **lactose malabsorption**.
- This test is a **non-invasive, definitive diagnostic tool** for lactose intolerance, directly assessing the inability to break down lactose.
*Normal small bowel histology*
- **Lactose intolerance** is due to a deficiency in the lactase enzyme, not a structural abnormality of the small bowel.
- Normal histology would be expected, but it does not directly confirm the enzyme deficiency or malabsorption.
*Symptom improvement on lactose-free diet*
- While supportive, symptom improvement on a **lactose-free diet** is a clinical observation and not a definitive diagnostic test.
- Other conditions might also improve with dietary changes, making it less specific than a breath test.
*Decreased lactase enzyme levels in duodenal biopsy*
- Measuring **lactase enzyme levels in a duodenal biopsy** is the most direct and accurate method for diagnosing lactase deficiency.
- However, it is an **invasive procedure**, making the non-invasive hydrogen breath test generally preferred as a strong diagnostic tool.
*Osmotic diarrhea with stool pH < 5.5*
- **Osmotic diarrhea** and **acidic stool (pH < 5.5)** are common findings in lactose intolerance due to unabsorbed lactose.
- These are **consequences** of lactose malabsorption rather than a direct diagnostic test for the condition itself, and can be seen in other malabsorptive states.
