Which of the following is a metabolic disorder inherited in an X-linked manner?
Q2
The major carrier of cholesterol in plasma is:
Q3
Identify the image and the disease it is associated with:
Q4
A patient diagnosed with an isolated increase in LDL, with a family history of the same disease in his father and brother, is likely to have a diagnosis of
Q5
A 4-year-old boy is brought to a pediatrician by his parents for a consultation after his teacher complained about his inability to focus or make friends at school. They mention that the boy does not interact well with others at home, school, or daycare. On physical examination, his vital signs are stable with normal weight, height, and head circumference for his age and sex. His general examination and neurologic examination are completely normal. A recent audiological evaluation shows normal hearing, and intellectual disability has been ruled out by a clinical psychologist. Which of the following investigations is indicated as part of his diagnostic evaluation at present?
Q6
A 4-year-old boy is brought to the physician for a well-child examination. He started walking at 20 months of age. He can use a cup to drink but cannot use silverware. He speaks in 2-word sentences and can build a tower of 4 blocks. He can scribble but cannot draw a circle. He is above the 99th percentile for height and at the 15th percentile for weight. Vital signs are within normal limits. Examination shows bilateral inferior lens dislocation. His fingers are long and slender. He has a high-arched palate. The thumb and 5th finger overlap when he grips a wrist with the opposite hand. The skin over the neck can be extended and stretched easily. Which of the following is the most likely cause of these findings?
Q7
A 52-year-old man is admitted directly from the clinic for a serum glucose of 980 mg/dL. He has had type 2 diabetes for 16 years, for which he was prescribed metformin and glimepiride; however, he reports not having followed his prescription due to its high cost. For the past 12 days, he has had excess urination, and has lost 6 kg in weight. He has also noted a progressively worsening cough productive of greenish-brown sputum for approximately 20 days. His temperature is 38.9°C (102.02°F), blood pressure is 97/62 mm Hg, pulse is 97/minute and respiratory rate is 26/minute. On physical examination, he is somnolent, his eyes are sunken, and there are crackles at the left lung base.
Lab results are shown:
Arterial pH: 7.33
Serum sodium: 130 mEq/L
Serum potassium: 3 mEq/L
Serum osmolality: 325 mOsm/kg
Serum beta-hydroxybutyrate: negative
Urinalysis: trace ketones
Intravenous normal saline infusion is started. Which of the following is the best next step in this patient?
Q8
The lac operon allows E. coli to effectively utilize lactose when it is available, and not to produce unnecessary proteins. Which of the following genes is constitutively expressed and results in the repression of the lac operon?
Q9
A researcher is studying physiologic and hormonal changes that occur during pregnancy. Specifically, they examine the behavior of progesterone over the course of the menstrual cycle and find that it normally decreases over time; however, during pregnancy this decrease does not occur in the usual time frame. The researcher identifies a circulating factor that appears to be responsible for this difference in progesterone behavior. In order to further examine this factor, the researcher denatures the circulating factor and examines the sizes of its components on a western blot as compared to several other hormones. One of the bands the researcher identifies in this circulating factor is identical to that of another known hormone with which of the following sites of action?
Q10
An investigator is studying the metabolism of an experimental drug that is known to have first order kinetics. Immediately after administering an intravenous dose of the drug to a patient, the serum concentration is 60 U/L. 3 hours later, the serum concentration of the drug is 30 U/L. 9 hours after administration, the serum concentration of the drug is most likely to be which of the following?
Disorders of Lipid Metabolism US Medical PG Practice Questions and MCQs
Question 1: Which of the following is a metabolic disorder inherited in an X-linked manner?
A. Duchenne muscular dystrophy
B. Adrenoleukodystrophy (Correct Answer)
C. Phenylketonuria
D. Marfan syndrome
Explanation: ***Adrenoleukodystrophy***
- **Adrenoleukodystrophy (ALD)** is an **X-linked recessive disorder** that affects the metabolism of very long-chain fatty acids (VLCFAs).
- It leads to the demyelination of nerve cells in the brain and spinal cord, as well as adrenal gland insufficiency.
*Phenylketonuria*
- **Phenylketonuria (PKU)** is an **autosomal recessive metabolic disorder** caused by a defect in the enzyme phenylalanine hydroxylase.
- It results in the accumulation of phenylalanine, leading to intellectual disability if not treated with a specialized diet.
*Duchenne muscular dystrophy*
- While **Duchenne muscular dystrophy (DMD)** is indeed an **X-linked recessive disorder**, it is primarily a muscle disorder, not a metabolic disorder in the classic sense.
- It involves a mutation in the **dystrophin gene**, leading to progressive muscle degeneration and weakness.
*Marfan syndrome*
- **Marfan syndrome** is an **autosomal dominant disorder** affecting connective tissue.
- It is caused by a mutation in the **FBN1 gene**, which codes for fibrillin-1, and primarily affects the skeletal, ocular, and cardiovascular systems.
Question 2: The major carrier of cholesterol in plasma is:
A. Very-Low-Density Lipoprotein (VLDL)
B. Low-Density Lipoprotein (LDL) (Correct Answer)
C. Chylomicrons
D. High-Density Lipoprotein (HDL)
Explanation: ***Low-Density Lipoprotein (LDL)***
- **LDL** is the **major carrier of cholesterol in plasma**, transporting approximately **60-70% of total plasma cholesterol**.
- It is primarily responsible for delivering **cholesterol** from the liver to peripheral tissues for **membrane synthesis**, **steroid hormone production**, and other cellular functions.
- LDL cholesterol levels are the primary target for cardiovascular risk assessment and management.
*Very-Low-Density Lipoprotein (VLDL)*
- **VLDL** primarily transports **triglycerides** (55-65% of its content) synthesized in the liver to peripheral tissues.
- While it contains some cholesterol (~10-15%), its main function is **triglyceride delivery**, and it serves as a precursor to LDL in the circulation.
*Chylomicrons*
- **Chylomicrons** are responsible for transporting **dietary triglycerides** and **cholesterol** from the intestines to tissues.
- They are the largest lipoproteins and primarily transport **exogenous (dietary) lipids**.
- Cholesterol represents only 3-5% of chylomicron content.
*High-Density Lipoprotein (HDL)*
- **HDL** carries approximately **20-30% of plasma cholesterol** and plays a crucial role in **reverse cholesterol transport**.
- It collects excess cholesterol from peripheral tissues and returns it to the liver for excretion.
- While functionally important for cholesterol homeostasis (protective against atherosclerosis), it carries significantly less cholesterol than LDL.
Question 3: Identify the image and the disease it is associated with:
A. Gaucher's disease (Correct Answer)
B. Tay-Sachs disease
C. Sandhoff's disease
D. Fabry's disease
Explanation: ***Gaucher's disease***
- The image shows **Gaucher cells** - characteristic lipid-laden macrophages with a distinctive **"crumpled tissue paper" or "wrinkled silk" cytoplasmic appearance** and eccentric nuclei [1]
- These cells are pathognomonic for **Gaucher's disease**, an **autosomal recessive lysosomal storage disorder** caused by **glucocerebrosidase deficiency** [1]
- Accumulation of **glucocerebroside** in macrophages creates the characteristic morphology seen in bone marrow, spleen, and liver [1]
- Caused by mutations in the *GBA* gene on chromosome 1 [1]
*Tay-Sachs disease*
- Autosomal recessive disorder caused by **hexosaminidase A deficiency** leading to **GM2 ganglioside accumulation** [2]
- Characteristic findings include **cherry-red spot on macula** and neuronal ballooning, not the macrophage changes seen in this image [2]
- Does not produce Gaucher cells
*Sandhoff's disease*
- Caused by deficiency of both **hexosaminidase A and B** due to *HEXB* gene mutations
- Similar to Tay-Sachs with GM2 ganglioside accumulation affecting neurons
- Does not produce the characteristic macrophage morphology shown in the image
*Fabry's disease*
- **X-linked recessive** disorder caused by **alpha-galactosidase A deficiency**
- Accumulation of **globotriaosylceramide** in vascular endothelial cells
- Histology may show lipid deposits in vessels and kidney, not the distinctive Gaucher cells seen here
**References:**
[1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 162-163.
[2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 161.
Question 4: A patient diagnosed with an isolated increase in LDL, with a family history of the same disease in his father and brother, is likely to have a diagnosis of
A. Abetalipoproteinemia
B. LDL receptor mutation (Correct Answer)
C. Familial type III hyperlipoproteinemia
D. Familial lipoprotein lipase deficiency
Explanation: ***LDL receptor mutation***
- An **isolated increase in LDL** with a strong **family history** (father and brother affected) is highly suggestive of **familial hypercholesterolemia**, which is most commonly caused by mutations in the **LDL receptor gene** [1].
- **LDL receptor mutations** lead to a reduced clearance of LDL from the blood, resulting in elevated LDL levels from birth [1].
*Familial type III hyperlipoproteinemia*
- This condition is characterized by elevated levels of both **cholesterol and triglycerides**, specifically involving **remnant lipoproteins** (IDL), not an isolated increase in LDL [2].
- It is often associated with **palmar xanthomas** and **tuberous xanthomas**, which are not mentioned in the patient's presentation.
*Abetalipoproteinemia*
- This is a rare genetic disorder characterized by the **absence of apolipoprotein B**, leading to very low or undetectable levels of **LDL, VLDL, and chylomicrons**.
- Patients typically present with **fat malabsorption, neurologic deficits**, and **retinitis pigmentosa**, which is contrary to an isolated increase in LDL.
*Familial lipoprotein lipase deficiency*
- This condition primarily causes a marked elevation in **chylomicrons and triglycerides** due to impaired clearance of triglyceride-rich lipoproteins.
- It does not present as an isolated increase in LDL and is often associated with **eruptive xanthomas**, **pancreatitis**, and **hepatosplenomegaly**.
Question 5: A 4-year-old boy is brought to a pediatrician by his parents for a consultation after his teacher complained about his inability to focus or make friends at school. They mention that the boy does not interact well with others at home, school, or daycare. On physical examination, his vital signs are stable with normal weight, height, and head circumference for his age and sex. His general examination and neurologic examination are completely normal. A recent audiological evaluation shows normal hearing, and intellectual disability has been ruled out by a clinical psychologist. Which of the following investigations is indicated as part of his diagnostic evaluation at present?
A. Magnetic resonance imaging (MRI) of brain
B. Electroencephalography
C. No further testing is needed
D. Positron Emission Tomography (PET) scanning of head
E. Autism spectrum disorder screening and developmental assessment (Correct Answer)
Explanation: ***Autism spectrum disorder screening and developmental assessment***
- The clinical presentation (inability to focus, difficulty making friends, poor social interaction across multiple settings) is **highly suggestive of Autism Spectrum Disorder (ASD)**.
- After ruling out **hearing impairment and intellectual disability**, the next appropriate step is **formal ASD screening using validated tools** such as the **Modified Checklist for Autism in Toddlers (M-CHAT)**, **Autism Diagnostic Observation Schedule (ADOS)**, or **Autism Diagnostic Interview-Revised (ADI-R)**.
- According to **AAP guidelines**, when developmental concerns suggestive of ASD are identified, formal screening and comprehensive developmental assessment are **essential components of the diagnostic evaluation**.
- ASD diagnosis is primarily **clinical**, based on standardized screening tools and developmental assessments, not neuroimaging or electrophysiological studies.
*No further testing is needed*
- This is **incorrect** because the patient has not yet undergone **formal ASD-specific screening and developmental assessment**.
- While hearing and intellectual disability have been ruled out, **diagnostic confirmation of ASD** requires structured evaluation using validated assessment tools.
- Simply observing symptoms without formal screening is inadequate for establishing an ASD diagnosis.
*Magnetic resonance imaging (MRI) of brain*
- Brain MRI is **not routinely indicated** for ASD diagnosis as it typically shows **normal findings** in children with ASD.
- Neuroimaging is reserved for cases with **focal neurological signs, regression, or atypical features** suggesting structural abnormalities.
- This patient has a **normal neurological examination**, making MRI unnecessary.
*Electroencephalography*
- EEG is indicated only when there is suspicion of **seizure disorder** or other specific neurological conditions.
- The patient has a **normal neurological examination** with no seizure-like symptoms, making EEG unnecessary at this stage.
*Positron Emission Tomography (PET) scanning of head*
- PET scans are **not part of routine ASD diagnostic workup** and are typically used in research settings or for evaluating specific metabolic or neoplastic conditions.
- The **radiation exposure and invasiveness** make PET scanning inappropriate for initial diagnostic evaluation in a child with developmental concerns.
Question 6: A 4-year-old boy is brought to the physician for a well-child examination. He started walking at 20 months of age. He can use a cup to drink but cannot use silverware. He speaks in 2-word sentences and can build a tower of 4 blocks. He can scribble but cannot draw a circle. He is above the 99th percentile for height and at the 15th percentile for weight. Vital signs are within normal limits. Examination shows bilateral inferior lens dislocation. His fingers are long and slender. He has a high-arched palate. The thumb and 5th finger overlap when he grips a wrist with the opposite hand. The skin over the neck can be extended and stretched easily. Which of the following is the most likely cause of these findings?
A. Hypoxanthine-guanine-phosphoribosyl transferase deficiency
B. Galactokinase deficiency
C. Fibrillin 1 deficiency
D. Cystathionine synthase deficiency (Correct Answer)
E. Type V collagen deficiency
Explanation: ***Cystathionine synthase deficiency***
- The combination of **inferior lens dislocation**, **marfanoid habitus** (tall stature, long slender fingers, high-arched palate), **developmental delay** (late walking, speech delay), and **hyperelastic skin** is highly suggestive of **homocystinuria** due to cystathionine synthase deficiency.
- **Homocystinuria** is an autosomal recessive disorder causing accumulation of **homocysteine**, leading to multisystem involvement.
*Hypoxanthine-guanine-phosphoribosyl transferase deficiency*
- This deficiency causes **Lesch-Nyhan syndrome**, characterized by **gout, intellectual disability, choreoathetosis, and self-mutilation**.
- It does not present with lens dislocation or marfanoid features.
*Galactokinase deficiency*
- This is a rare form of **galactosemia** primarily causing **cataracts**.
- It does not explain the developmental delay, marfanoid features, or lens dislocation.
*Fibrillin 1 deficiency*
- This causes **Marfan syndrome**, which shares features like **tall stature, long slender fingers, high-arched palate, and lens dislocation**.
- However, in Marfan syndrome, lens dislocation is typically **superior**, while in this case, it is **inferior**, pointing towards homocystinuria.
*Type V collagen deficiency*
- This can be associated with **Ehlers-Danlos syndrome**, which features **hyperelastic skin** and joint hypermobility.
- However, it does not typically cause lens dislocation or the specific marfanoid habitus described, and developmental delay is not a primary feature.
Question 7: A 52-year-old man is admitted directly from the clinic for a serum glucose of 980 mg/dL. He has had type 2 diabetes for 16 years, for which he was prescribed metformin and glimepiride; however, he reports not having followed his prescription due to its high cost. For the past 12 days, he has had excess urination, and has lost 6 kg in weight. He has also noted a progressively worsening cough productive of greenish-brown sputum for approximately 20 days. His temperature is 38.9°C (102.02°F), blood pressure is 97/62 mm Hg, pulse is 97/minute and respiratory rate is 26/minute. On physical examination, he is somnolent, his eyes are sunken, and there are crackles at the left lung base.
Lab results are shown:
Arterial pH: 7.33
Serum sodium: 130 mEq/L
Serum potassium: 3 mEq/L
Serum osmolality: 325 mOsm/kg
Serum beta-hydroxybutyrate: negative
Urinalysis: trace ketones
Intravenous normal saline infusion is started. Which of the following is the best next step in this patient?
A. Adding sodium bicarbonate infusion
B. Starting basal-bolus insulin
C. Adding dopamine infusion
D. Adding potassium to the intravenous fluids (Correct Answer)
E. Starting regular insulin infusion
Explanation: ***Adding potassium to the intravenous fluids***
- This patient presents with **hypokalemia** (serum potassium 3 mEq/L) and is receiving aggressive fluid resuscitation, which will further dilute his potassium and drive potassium into cells, potentially worsening the hypokalemia. **Potassium replacement** is critical to prevent cardiac arrhythmias.
- While fluids and insulin will be necessary, **correcting potassium** should be initiated early, especially with symptoms of hypokalemia or if the level is <3.3 mEq/L, to prevent serious complications and before starting insulin.
*Adding sodium bicarbonate infusion*
- The patient's arterial pH of 7.33 indicates only **mild acidosis**, likely due to hypovolemic lactic acidosis or other underlying issues, but not severe enough to warrant bicarbonate infusion.
- Additionally, his serum beta-hydroxybutyrate is negative and ketones are only trace, ruling out **diabetic ketoacidosis (DKA)**, which is typically the primary indication for bicarbonate in diabetic emergencies.
*Starting basal-bolus insulin*
- The patient requires insulin for his **hyperglycemia**, but **basal-bolus insulin** is usually started once the patient is stable, able to eat, and out of the acute hyperosmolar state.
- In this emergency setting, **intravenous regular insulin infusion** is preferred for precise titration and rapid glucose control.
*Adding dopamine infusion*
- Dopamine is a **vasopressor** used to support blood pressure in cases of **hypotensive shock** refractory to fluid resuscitation.
- While the patient is hypotensive (BP 97/62 mm Hg), his primary problem is severe dehydration, so initial management focuses on **fluid resuscitation** with normal saline rather than immediate pressors.
*Starting regular insulin infusion*
- While **regular insulin infusion** is appropriate for managing severe hyperglycemia in hyperosmolar hyperglycemic state (HHS), it should be initiated **after initial fluid resuscitation** and after ensuring potassium is ≥3.3 mEq/L.
- Administering insulin without adequate potassium replacement could precipitate severe and life-threatening **hypokalemia**, as insulin drives potassium into cells.
Question 8: The lac operon allows E. coli to effectively utilize lactose when it is available, and not to produce unnecessary proteins. Which of the following genes is constitutively expressed and results in the repression of the lac operon?
A. LacY
B. LacI (Correct Answer)
C. LacZ
D. CAP
E. LacA
Explanation: ***LacI***
- The **LacI gene** encodes the **Lac repressor protein**, which is constitutively expressed (always produced) and binds to the operator region of the lac operon.
- When bound, the **Lac repressor** blocks RNA polymerase from transcribing the structural genes (LacZ, LacY, LacA), thereby repressing the operon in the absence of lactose.
*LacY*
- The **LacY gene** encodes **lactose permease**, an enzyme responsible for transporting lactose into the bacterial cell.
- Its expression is regulated by the lac operon and is not constitutively expressed; rather, it is induced in the presence of lactose.
*LacZ*
- The **LacZ gene** encodes **beta-galactosidase**, the enzyme that breaks down lactose into glucose and galactose.
- Like LacY, its expression is part of the lac operon and is induced when lactose is available, not expressed constitutively.
*CAP*
- **CAP (Catabolite Activator Protein)** is a regulatory protein that, when bound to cAMP, activates transcription of the lac operon when glucose is absent.
- While essential for lac operon regulation, CAP is not a gene whose constitutive expression leads to repression of the operon.
*LacA*
- The **LacA gene** encodes **thiogalactoside transacetylase**, an enzyme with a less clear role in lactose metabolism but is part of the lac operon.
- Its expression is also regulated and induced along with LacZ and LacY, not constitutively expressed to repress the operon.
Question 9: A researcher is studying physiologic and hormonal changes that occur during pregnancy. Specifically, they examine the behavior of progesterone over the course of the menstrual cycle and find that it normally decreases over time; however, during pregnancy this decrease does not occur in the usual time frame. The researcher identifies a circulating factor that appears to be responsible for this difference in progesterone behavior. In order to further examine this factor, the researcher denatures the circulating factor and examines the sizes of its components on a western blot as compared to several other hormones. One of the bands the researcher identifies in this circulating factor is identical to that of another known hormone with which of the following sites of action?
A. Thyroid gland (Correct Answer)
B. Adrenal gland
C. Adipocytes
D. Bones
E. Kidney tubules
Explanation: ***Correct: Thyroid gland***
- The circulating factor described is **human chorionic gonadotropin (hCG)**, which maintains the corpus luteum and progesterone production during early pregnancy
- hCG is a **glycoprotein hormone** composed of an **α subunit** and a **β subunit**
- The **α subunit of hCG is identical** to the α subunits of **TSH (thyroid-stimulating hormone)**, **LH (luteinizing hormone)**, and **FSH (follicle-stimulating hormone)**
- When denatured and examined on Western blot, one of the bands (the α subunit) would be identical to that of **TSH**
- **TSH acts on the thyroid gland** to stimulate thyroid hormone synthesis and release
- This structural similarity explains why very high levels of hCG (as in molar pregnancy or hyperemesis gravidarum) can sometimes cause **thyrotoxicosis** due to cross-reactivity with TSH receptors
*Incorrect: Adrenal gland*
- **ACTH (adrenocorticotropic hormone)** acts on the adrenal cortex to stimulate cortisol production
- ACTH is a **peptide hormone** derived from POMC (pro-opiomelanocortin) and does **NOT share any structural components** with hCG
- There is no identical band between hCG and ACTH on Western blot
*Incorrect: Adipocytes*
- Adipocytes are regulated by hormones like **insulin** and **leptin**
- Neither of these hormones share structural components with hCG
*Incorrect: Bones*
- Bones are primarily regulated by **PTH (parathyroid hormone)**, **calcitonin**, and **vitamin D**
- None of these hormones share structural components with hCG
*Incorrect: Kidney tubules*
- Kidney tubules are regulated by **ADH (antidiuretic hormone/vasopressin)** and **aldosterone**
- Neither shares structural components with hCG
Question 10: An investigator is studying the metabolism of an experimental drug that is known to have first order kinetics. Immediately after administering an intravenous dose of the drug to a patient, the serum concentration is 60 U/L. 3 hours later, the serum concentration of the drug is 30 U/L. 9 hours after administration, the serum concentration of the drug is most likely to be which of the following?
A. 5 U/L
B. 0 U/L
C. 15 U/L
D. 7.5 U/L (Correct Answer)
E. 3.75 U/L
Explanation: ***7.5 U/L***
- The drug follows **first-order kinetics**, meaning a constant fraction of the drug is eliminated per unit time, resulting in a constant **half-life**.
- The concentration halved from 60 U/L to 30 U/L in 3 hours, indicating a **half-life of 3 hours**. Thus, after another 3 hours (total 6 hours), the concentration would be 15 U/L, and after yet another 3 hours (total 9 hours), it would be **7.5 U/L**.
*5 U/L*
- This answer suggests a slower rate of elimination than calculated for first-order kinetics with a 3-hour half-life.
- If the half-life were longer than 3 hours, then 5 U/L might be a plausible concentration at 9 hours.
*0 U/L*
- For drugs following **first-order kinetics**, the concentration approaches zero asymptotically and never truly reaches zero within a finite timeframe, unless the total elimination has significantly exceeded multiple half-lives.
- This answer indicates complete elimination, which is incorrect for a drug still undergoing elimination after 9 hours.
*15 U/L*
- This would be the concentration at 6 hours (two half-lives) after administration, not 9 hours (three half-lives).
- It would occur if only two half-life periods had passed instead of three.
*3.75 U/L*
- This value represents the concentration after a fourth half-life (12 hours), not three half-lives (9 hours).
- This would be the concentration after 12 hours had passed from the initial administration.
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