A six-month-old infant presents with chronic, persistent diarrhea, oral thrush, and a severe diaper rash. The infant was treated four weeks ago for an upper respiratory and ear infection. A family history is significant for a consanguineous relationship between the mother and father. Physical examination demonstrates the absence of palpable lymph nodes. Accumulation of which of the following would lead to this disease phenotype?
Q172
Which of the following factors gives the elastin molecule the ability to stretch and recoil?
Q173
A 4-year-old girl is brought to the physician for a routine checkup. She was recently adopted and has never seen a doctor before. The patient's parents state she was very emaciated when they adopted her and noticed she has trouble seeing in the evening. They also noted that she was experiencing profuse foul-smelling diarrhea as well, which is currently being worked up by a gastroenterologist. Her temperature is 97.8°F (36.6°C), blood pressure is 104/54 mmHg, pulse is 100/min, respirations are 19/min, and oxygen saturation is 98% on room air. The girl appears very thin. She has dry skin noted on physical exam. Laboratory studies are ordered as seen below.
Hemoglobin: 12 g/dL
Hematocrit: 36%
Leukocyte count: 4,500/mm^3 with normal differential
Platelet count: 191,000/mm^3
Serum:
Na+: 139 mEq/L
Cl-: 100 mEq/L
K+: 3.8 mEq/L
HCO3-: 28 mEq/L
BUN: 20 mg/dL
Glucose: 88 mg/dL
Creatinine: 0.7 mg/dL
Ca2+: 9.0 mg/dL
Which of the following findings is also likely to be seen in this patient?
Q174
A 56-year old man is brought in by ambulance to the emergency department and presents with altered consciousness, confabulation, and widespread rash. He is recognized as a homeless man that lives in the area with a past medical history is significant for traumatic brain injury 4 years ago and chronic gastritis. He also has a long history of alcohol abuse. His vital signs are as follows: blood pressure 140/85 mm Hg, heart rate 101/min, respiratory rate 15/min, and temperature 36.1°C (97.0°F). His weight is 56 kg (123.5 lb) and height is 178 cm (5.8 ft). The patient is lethargic and his speech is incoherent. Examination reveals gingival bleeding, scattered corkscrew body hair, bruises over the forearms and abdomen, multiple petechiae, and perifollicular, hyperkeratotic papules over his extremities. His lung and heart sounds are normal. Abdominal palpation reveals tenderness over the epigastric area and hepatomegaly. Neurologic examination demonstrates symmetrically diminished reflexes in the lower extremities. Impairment of which of the following processes is the most likely cause of this patient’s hyperkeratotic rash?
Q175
A 1-week-old male newborn is brought to the physician for a follow-up examination after the results of newborn screening showed an increased serum concentration of phenylalanine. Genetic analysis confirms a diagnosis of phenylketonuria. The physician counsels the patient's family on the recommended dietary restrictions, including avoidance of artificial sweeteners that contain aspartame. Aspartame is a molecule composed of aspartate and phenylalanine and its digestion can lead to hyperphenylalaninemia in patients with phenylketonuria. Which of the following enzymes is primarily responsible for the breakdown of aspartame?
Q176
An American doctor is on an outreach trip to visit local communities in Ethiopia. In one clinic, he found many cases of children ages 2–5 years who have significantly low weight and height for their age. These children also had pale sclerae, distended abdomens, dermatoses, and marked edema in the lower extremities. Malnutrition in these patients is investigated and classified as (kwashiorkor) protein malnutrition. Appropriate nutrition supplementation was ordered and shipped in for the affected families. Which of the following amino acids must be included for these patients?
Q177
A mother with HIV has given birth to a healthy boy 2 days ago. She takes her antiretroviral medication regularly and is compliant with the therapy. Before being discharged, her doctor explains that she cannot breastfeed the child since there is a risk of infection through breastfeeding and stresses that the child can benefit from formula feeding. The physician stresses the importance of not overheating the formula since Vitamin C may be inactivated by overheating. Which process could be impaired if the mother boiled the formula longer than needed?
Q178
A 25-year-old man presents to the emergency department after fainting at his investment banking office. He states that he has experienced intermittent headaches since high school, but has never fainted. He reports eating multiple small meals regularly throughout the day. He further notes that multiple family members have frequently complained about headaches. Physical exam reveals a well-nourished, well-built, afebrile man with BP 170/80, HR 55, RR 10. Chemistries reveal Na 147, K 3, Cl 110, HCO3 30, BUN 25, Cr 1.1, glucose 120. A biopsy of the tissue most likely at issue in this patient will reveal the most abnormal cellular amounts of which of the following?
Q179
A 54-year-old man is brought to the emergency department by his wife because of progressive nausea, vomiting, and right-sided flank pain for 2 days. The pain is colicky and radiates to the groin. He has a history of gout and type 2 diabetes mellitus. Current medications are metformin and allopurinol. He recently began taking large amounts of a multivitamin supplement after he read on the internet that it may help to prevent gout attacks. Physical examination shows right-sided costovertebral angle tenderness. Oral examination shows dental erosions. A CT scan of the abdomen shows an 8-mm stone in the right proximal ureter. Microscopic examination of a urine sample shows bipyramidal, envelope-shaped crystals. An increased serum concentration of which of the following is the most likely cause of this patient’s symptoms?
Q180
A 1-year-old boy is brought to his pediatrician for a follow-up appointment. He was recently diagnosed with failure to thrive and developmental delay. His weight is 7 kg (15.4 lb), height is 61 cm (24 in), and head circumference is 42 cm (16.5 in). The patient’s father had a younger sister who suffered from mental and physical delay and died at a very young age. The patient was able to raise his head at the age of 7 months and began to sit alone only recently. He babbles, coos, and smiles to other people. On presentation, his blood pressure is 75/40 mm Hg, heart rate is 147/min, respiratory rate is 28/min, and temperature is 36.4°C (97.5°F). He has a coarse face with small deep orbits, proptotic eyes, big lips, and gingival hyperplasia. His skin is pale with decreased elasticity. His lung and heart sounds are normal. Abdominal examination reveals diminished anterior abdominal wall muscle tone and hepatomegaly. Muscle tone is increased in all groups of muscles on both upper and lower extremities. The physician becomes concerned and performs testing for the suspected hereditary disease. A blood test shows increased lysosomal enzyme concentration in the serum and decreased N-acetylglucosamine-1-phosphotransferase (GlcNAc phosphotransferase) activity within the leukocytes. Which of the statements listed below describes the mechanism of the patient’s condition?
Metabolism US Medical PG Practice Questions and MCQs
Question 171: A six-month-old infant presents with chronic, persistent diarrhea, oral thrush, and a severe diaper rash. The infant was treated four weeks ago for an upper respiratory and ear infection. A family history is significant for a consanguineous relationship between the mother and father. Physical examination demonstrates the absence of palpable lymph nodes. Accumulation of which of the following would lead to this disease phenotype?
A. Sphingomyelin
B. Deoxyadenosine (Correct Answer)
C. Ceramide trihexoside
D. Phenylalanine
E. Galactitol
Explanation: ***Deoxyadenosine***
- The constellation of chronic infections (oral thrush, severe diaper rash suggesting recurrent infections), persistent diarrhea, and the absence of palpable lymph nodes in an infant with consanguineous parents points to a **severe combined immunodeficiency (SCID)**.
- **Adenosine deaminase (ADA) deficiency** is a cause of SCID, leading to the accumulation of **deoxyadenosine** which is toxic to lymphocytes, causing their severe depletion and subsequent immunodeficiency.
*Sphingomyelin*
- Accumulation of **sphingomyelin** occurs in **Niemann-Pick disease**, a lysosomal storage disorder.
- This condition presents with **hepatosplenomegaly**, neurodegeneration, and a **cherry-red spot** on the macula, symptoms not described here.
*Ceramide trihexoside*
- The accumulation of **ceramide trihexoside** is characteristic of **Fabry disease**.
- Fabry disease typically presents with **neuropathic pain**, angiokeratomas, and renal/cardiac involvement, not immunodeficiency.
*Phenylalanine*
- Accumulation of **phenylalanine** is the hallmark of **phenylketonuria (PKU)**.
- PKU leads to severe neurological developmental issues if untreated but does not cause immunodeficiency.
*Galactitol*
- The accumulation of **galactitol** is associated with **galactosemia**.
- This condition presents with **cataracts**, hepatomegaly, and developmental delay, but not immunodeficiency or recurrent infections as seen in this infant.
Question 172: Which of the following factors gives the elastin molecule the ability to stretch and recoil?
A. Elastase activity
B. Triple helix formation
C. Cross-links between lysine residues (Correct Answer)
D. Cleavage of disulfide rich terminal regions
E. Hydroxylation of proline and lysine rich regions
Explanation: ***Cross-links between lysine residues***
- The extensive **crosslinking** between **lysine residues** in elastin forms a rubber-like network that allows the molecule to stretch under tension and recoil to its original shape.
- These cross-links are formed by specialized amino acids, such as **desmosin** and **isodesmosin**, derived from multiple lysine residues, creating a stable yet flexible structure.
*Elastase activity*
- **Elastase** is an enzyme that **degrades elastin**, breaking down its structure rather than contributing to its elastic properties.
- Increased elastase activity can lead to conditions like **emphysema**, where the loss of elastin's elasticity impairs lung function.
*Triple helix formation*
- **Triple helix formation** is characteristic of **collagen**, providing it with tensile strength and rigidity, rather than the stretch and recoil properties of elastin.
- Elastin's structure is largely amorphous, allowing for greater flexibility compared to collagen's rigid helical organization.
*Cleavage of disulfide rich terminal regions*
- While some proteins utilize **disulfide bonds** for structural integrity, **elastin's elasticity** is primarily due to its cross-linked lysine network, not disulfide bond cleavage.
- The formation or cleavage of disulfide bonds is not the primary mechanism by which elastin exerts its characteristic stretch and recoil.
*Hydroxylation of proline and lysine rich regions*
- **Hydroxylation of proline and lysine residues** is a crucial post-translational modification for **collagen stability** (e.g., in vitamin C deficiency leading to scurvy) but is not a defining feature of elastin's elasticity.
- Elastin contains fewer hydroxyproline residues and no hydroxylysine, distinguishing it from collagen's structure and function.
Question 173: A 4-year-old girl is brought to the physician for a routine checkup. She was recently adopted and has never seen a doctor before. The patient's parents state she was very emaciated when they adopted her and noticed she has trouble seeing in the evening. They also noted that she was experiencing profuse foul-smelling diarrhea as well, which is currently being worked up by a gastroenterologist. Her temperature is 97.8°F (36.6°C), blood pressure is 104/54 mmHg, pulse is 100/min, respirations are 19/min, and oxygen saturation is 98% on room air. The girl appears very thin. She has dry skin noted on physical exam. Laboratory studies are ordered as seen below.
Hemoglobin: 12 g/dL
Hematocrit: 36%
Leukocyte count: 4,500/mm^3 with normal differential
Platelet count: 191,000/mm^3
Serum:
Na+: 139 mEq/L
Cl-: 100 mEq/L
K+: 3.8 mEq/L
HCO3-: 28 mEq/L
BUN: 20 mg/dL
Glucose: 88 mg/dL
Creatinine: 0.7 mg/dL
Ca2+: 9.0 mg/dL
Which of the following findings is also likely to be seen in this patient?
A. Xerophthalmia (Correct Answer)
B. Cheilosis
C. Ataxia
D. Perifollicular hemorrhages
E. Diarrhea
Explanation: **Xerophthalmia**
- The patient's history of **malnutrition** and **night blindness** strongly suggests **vitamin A deficiency**, which can lead to **xerophthalmia** (dry eyes and corneal damage).
- Her **foul-smelling diarrhea** indicates **fat malabsorption**, which impairs the absorption of fat-soluble vitamins, including **vitamin A**.
*Cheilosis*
- **Cheilosis** (cracking at the corners of the mouth) is primarily a symptom of **riboflavin (vitamin B2)** or **pyridoxine (vitamin B6)** deficiency.
- While the patient is malnourished, the specific symptoms point more directly to a fat-soluble vitamin deficiency.
*Ataxia*
- **Ataxia** (lack of voluntary coordination of muscle movements) is a neurological symptom associated with **vitamin B12** or **vitamin E deficiency**.
- While possible in severe malnutrition, it is not directly linked to the presented symptoms of night blindness and dry skin.
*Perifollicular hemorrhages*
- **Perifollicular hemorrhages** (small bruising especially around hair follicles) are characteristic of **scurvy**, caused by severe **vitamin C deficiency**.
- The patient's symptoms do not align with scurvy, which typically presents with bleeding gums, poor wound healing, and joint pain.
*Diarrhea*
- The patient is already described as experiencing **profuse foul-smelling diarrhea**, which is being worked up by a gastroenterologist.
- The question asks for an additional finding likely to be seen, not a symptom already present.
Question 174: A 56-year old man is brought in by ambulance to the emergency department and presents with altered consciousness, confabulation, and widespread rash. He is recognized as a homeless man that lives in the area with a past medical history is significant for traumatic brain injury 4 years ago and chronic gastritis. He also has a long history of alcohol abuse. His vital signs are as follows: blood pressure 140/85 mm Hg, heart rate 101/min, respiratory rate 15/min, and temperature 36.1°C (97.0°F). His weight is 56 kg (123.5 lb) and height is 178 cm (5.8 ft). The patient is lethargic and his speech is incoherent. Examination reveals gingival bleeding, scattered corkscrew body hair, bruises over the forearms and abdomen, multiple petechiae, and perifollicular, hyperkeratotic papules over his extremities. His lung and heart sounds are normal. Abdominal palpation reveals tenderness over the epigastric area and hepatomegaly. Neurologic examination demonstrates symmetrically diminished reflexes in the lower extremities. Impairment of which of the following processes is the most likely cause of this patient’s hyperkeratotic rash?
A. Carboxylation of clotting factors
B. Hydroxylation of proline residues (Correct Answer)
C. Ethanol oxidation to acetaldehyde
D. Decarboxylation of histidine
E. Deamination of guanine
Explanation: ***Hydroxylation of proline residues***
- The patient's presentation with **perifollicular, hyperkeratotic papules**, corkscrew hair, gingival bleeding, petechiae, and bruising, along with a history of alcohol abuse and homelessness, is highly suggestive of **scurvy** (vitamin C deficiency).
- **Vitamin C** (ascorbic acid) is a crucial cofactor for the **hydroxylation of proline and lysine residues** during **collagen synthesis**. Impaired hydroxylation leads to defective collagen, affecting blood vessel integrity and skin structure, causing the observed signs.
*Carboxylation of clotting factors*
- This process is dependent on **vitamin K**, not vitamin C.
- A deficiency in vitamin K would typically present with a bleeding diathesis due to impaired production of functional **clotting factors II, VII, IX, and X**, but would not cause the specific skin manifestations like perifollicular hyperkeratosis or corkscrew hairs.
*Ethanol oxidation to acetaldehyde*
- This is a metabolic pathway primarily involving **alcohol dehydrogenase** and **aldehyde dehydrogenase**, which are not directly dependent on vitamin C.
- While chronic alcohol abuse can lead to various nutritional deficiencies, including vitamin C, this specific enzymatic process is not the direct cause of the skin findings described.
*Decarboxylation of histidine*
- This process leads to the formation of **histamine**, a crucial mediator in allergic and inflammatory responses.
- While histamine plays a role in skin inflammation, the decarboxylation of histidine is not directly linked to the pathology of scurvy or the formation of hyperkeratotic papules and corkscrew hairs.
*Deamination of guanine*
- This is a process involved in **nucleic acid metabolism** and can occur spontaneously or via enzymatic pathways.
- While relevant to DNA integrity and repair, it is unrelated to the biochemical function of vitamin C in collagen synthesis or the clinical manifestations of scurvy.
Question 175: A 1-week-old male newborn is brought to the physician for a follow-up examination after the results of newborn screening showed an increased serum concentration of phenylalanine. Genetic analysis confirms a diagnosis of phenylketonuria. The physician counsels the patient's family on the recommended dietary restrictions, including avoidance of artificial sweeteners that contain aspartame. Aspartame is a molecule composed of aspartate and phenylalanine and its digestion can lead to hyperphenylalaninemia in patients with phenylketonuria. Which of the following enzymes is primarily responsible for the breakdown of aspartame?
A. Carboxypeptidase A
B. Dipeptidase (Correct Answer)
C. Pepsin
D. Trypsin
E. Chymotrypsin
Explanation: ***Dipeptidase***
- Aspartame is a **dipeptide methyl ester** composed of two amino acids (aspartate and phenylalanine) linked by a peptide bond.
- **Dipeptidases** are brush border enzymes primarily responsible for hydrolyzing the **peptide bond** in dipeptides into their constituent amino acids, which releases phenylalanine from aspartame.
- While esterases also act on aspartame to remove the methyl ester group, dipeptidases perform the critical peptide bond cleavage that releases free phenylalanine.
*Carboxypeptidase A*
- **Carboxypeptidase A** is a pancreatic exopeptidase that cleaves amino acids from the **carboxyl-terminal** end of polypeptide chains.
- While it acts on peptide bonds, its primary function is on longer peptides, not specifically on dipeptides like aspartame.
*Pepsin*
- **Pepsin** is a major enzyme in the stomach responsible for initiating protein digestion by cleaving peptide bonds, primarily between aromatic amino acids and other residues.
- It works optimally at an **acidic pH** and mainly breaks down large proteins into smaller polypeptides, not dipeptides.
*Trypsin*
- **Trypsin** is a pancreatic serine protease that cleaves peptide bonds on the carboxyl side of **lysine** and **arginine** residues in polypeptides.
- It is an important enzyme for protein digestion in the small intestine but does not specifically break down dipeptides.
*Chymotrypsin*
- **Chymotrypsin** is another pancreatic serine protease that cleaves peptide bonds on the carboxyl side of **tyrosine**, **tryptophan**, and **phenylalanine** residues.
- While it acts on phenylalanine-containing peptides, its main role is in breaking down larger polypeptides, not simple dipeptides like aspartame.
Question 176: An American doctor is on an outreach trip to visit local communities in Ethiopia. In one clinic, he found many cases of children ages 2–5 years who have significantly low weight and height for their age. These children also had pale sclerae, distended abdomens, dermatoses, and marked edema in the lower extremities. Malnutrition in these patients is investigated and classified as (kwashiorkor) protein malnutrition. Appropriate nutrition supplementation was ordered and shipped in for the affected families. Which of the following amino acids must be included for these patients?
A. Tyrosine
B. Methionine (Correct Answer)
C. Arginine
D. Alanine
E. Glutamine
Explanation: ***Methionine***
- **Methionine is an essential amino acid**, meaning it **cannot be synthesized by the body** and **must be obtained from the diet**. In kwashiorkor (protein malnutrition), supplementation with essential amino acids is critical.
- Methionine is particularly important for the synthesis of **lipoproteins**, which are necessary for the transport of lipids from the liver. Its deficiency contributes to the **fatty liver** commonly seen in kwashiorkor.
- Among the options listed, methionine is the **only essential amino acid** that must be included in nutritional supplementation.
*Tyrosine*
- **Tyrosine** is a **non-essential amino acid**, meaning the body can synthesize it from the essential amino acid phenylalanine.
- While important for catecholamine and thyroid hormone synthesis, it is **not required in the diet** as long as adequate phenylalanine is provided.
*Arginine*
- **Arginine** is a **conditionally essential amino acid**, typically synthesized adequately by the body except in certain conditions (growth, illness, stress).
- While it plays roles in the urea cycle and nitric oxide synthesis, it is **not absolutely essential** in dietary supplementation for kwashiorkor in the way that essential amino acids are.
*Alanine*
- **Alanine** is a **non-essential amino acid** involved in the glucose-alanine cycle and nitrogen transport from muscle to liver.
- The body can readily synthesize alanine, so it is **not required in dietary supplementation**.
*Glutamine*
- **Glutamine** is a **conditionally essential amino acid**, especially important for enterocyte health, immune function, and nitrogen transport.
- While beneficial for gut integrity and recovery in malnutrition, it can be synthesized by the body and is **not absolutely essential** in the diet like methionine.
Question 177: A mother with HIV has given birth to a healthy boy 2 days ago. She takes her antiretroviral medication regularly and is compliant with the therapy. Before being discharged, her doctor explains that she cannot breastfeed the child since there is a risk of infection through breastfeeding and stresses that the child can benefit from formula feeding. The physician stresses the importance of not overheating the formula since Vitamin C may be inactivated by overheating. Which process could be impaired if the mother boiled the formula longer than needed?
A. Heme synthesis
B. Collagen synthesis (Correct Answer)
C. Purine synthesis
D. Protein catabolism
E. Fatty acid metabolism
Explanation: ***Collagen synthesis***
- **Vitamin C** is essential for the hydroxylation of proline and lysine residues, which is a crucial step in the maturation and cross-linking of **collagen fibers**.
- Without adequate vitamin C, collagen synthesis is impaired, leading to weakened connective tissues and conditions like **scurvy**.
- This is the **primary and most direct** metabolic role of vitamin C.
*Heme synthesis*
- **Heme synthesis** primarily involves a series of enzymatic steps occurring in the mitochondria and cytosol, with key enzymes like **ALA synthase** and **ferrochelatase**.
- While **vitamin C** enhances iron absorption and helps reduce ferric iron (Fe³⁺) to ferrous iron (Fe²⁺), it is not a direct cofactor in the enzymatic pathway of heme formation itself.
- Vitamin C deficiency would **not directly impair** the heme synthesis pathway enzymes.
*Purine synthesis*
- **Purine synthesis** is a complex pathway that produces adenine and guanine nucleotides, primarily driven by enzymes like **PRPP amidotransferase** and requiring cofactors such as **folate**.
- **Vitamin C** does not directly participate as a cofactor or substrate in the de novo synthesis of purines.
*Protein catabolism*
- **Protein catabolism** involves the breakdown of proteins into amino acids and their further degradation, mainly through the **ubiquitin-proteasome system** or lysosomal pathways.
- **Vitamin C** is not directly involved in the enzymatic processes that govern the breakdown of proteins.
*Fatty acid metabolism*
- **Fatty acid metabolism** includes synthesis (lipogenesis) and breakdown (beta-oxidation) of fatty acids, processes heavily reliant on coenzymes like **NADPH** and **FAD**, and involving mitochondrial enzymes.
- While vitamin C acts as an antioxidant, it does not play a direct role in the enzymatic pathways of **fatty acid synthesis** or degradation.
Question 178: A 25-year-old man presents to the emergency department after fainting at his investment banking office. He states that he has experienced intermittent headaches since high school, but has never fainted. He reports eating multiple small meals regularly throughout the day. He further notes that multiple family members have frequently complained about headaches. Physical exam reveals a well-nourished, well-built, afebrile man with BP 170/80, HR 55, RR 10. Chemistries reveal Na 147, K 3, Cl 110, HCO3 30, BUN 25, Cr 1.1, glucose 120. A biopsy of the tissue most likely at issue in this patient will reveal the most abnormal cellular amounts of which of the following?
A. smooth endoplasmic reticulum (Correct Answer)
B. peroxisome
C. lysosome
D. rough endoplasmic reticulum
E. beta-adrenergic receptor
Explanation: ***smooth endoplasmic reticulum***
- This patient presents with **hypertension** (BP 170/80), **hypokalemia** (K 3), **metabolic alkalosis** (HCO3 30), and hyperglycemia, which are classic findings of **primary hyperaldosteronism** (Conn syndrome), typically caused by an adrenal cortical adenoma.
- The adrenal cortex synthesizes **steroid hormones** (aldosterone, cortisol, androgens) from cholesterol. This process occurs in the **smooth endoplasmic reticulum** and mitochondria, where enzymes like cytochrome P450s are localized.
- A biopsy of an aldosterone-producing adenoma would reveal **markedly increased smooth endoplasmic reticulum** to accommodate the enhanced steroid hormone synthesis. The smooth ER contains the enzymatic machinery for steroid biosynthesis.
*peroxisome*
- Peroxisomes are involved in **β-oxidation of very long-chain fatty acids**, plasmalogen synthesis, and detoxification reactions.
- While present in adrenal cells, they do not play a primary role in steroid hormone synthesis and would not be abnormally increased in an aldosterone-producing adenoma.
*lysosome*
- Lysosomes contain **hydrolytic enzymes** for degradation of cellular waste and macromolecules.
- Increased lysosomes are characteristic of **lysosomal storage diseases**, not hormone-secreting tumors of the adrenal cortex.
- They are not involved in steroid hormone biosynthesis.
*rough endoplasmic reticulum*
- The rough ER synthesizes **secreted and membrane proteins** via ribosome-mediated translation.
- While some increase might occur in any proliferating tumor, steroid hormones are **lipid-derived molecules**, not proteins, so their synthesis does not primarily involve the rough ER.
- The smooth ER, not rough ER, is the key organelle for steroid biosynthesis.
*beta-adrenergic receptor*
- Beta-adrenergic receptors are **cell surface receptors** that respond to catecholamines (epinephrine, norepinephrine).
- They are not organelles and would not be abnormally increased within cells of an aldosterone-producing adenoma.
- This option would be relevant for catecholamine-responsive tissues, not steroid-producing tumors.
Question 179: A 54-year-old man is brought to the emergency department by his wife because of progressive nausea, vomiting, and right-sided flank pain for 2 days. The pain is colicky and radiates to the groin. He has a history of gout and type 2 diabetes mellitus. Current medications are metformin and allopurinol. He recently began taking large amounts of a multivitamin supplement after he read on the internet that it may help to prevent gout attacks. Physical examination shows right-sided costovertebral angle tenderness. Oral examination shows dental erosions. A CT scan of the abdomen shows an 8-mm stone in the right proximal ureter. Microscopic examination of a urine sample shows bipyramidal, envelope-shaped crystals. An increased serum concentration of which of the following is the most likely cause of this patient’s symptoms?
A. Vitamin C (Correct Answer)
B. Vitamin B3
C. Vitamin A
D. Vitamin E
E. Uric acid
Explanation: ***Vitamin C***
- The patient presents with **renal colic** due to a ureteral stone, and urine microscopy shows **bipyramidal, envelope-shaped crystals**, which are characteristic of calcium oxalate crystals.
- Excessive intake of **Vitamin C (ascorbic acid)** is metabolized into **oxalate**, significantly increasing the risk of **calcium oxalate stone formation**.
*Vitamin B3*
- **Vitamin B3 (niacin)** supplementation can cause flushing, itching, and gastrointestinal upset but is not directly associated with **calcium oxalate kidney stone formation**.
- It is sometimes used for **dyslipidemia**, but there's no link to kidney stones or the specific crystal morphology described.
*Vitamin A*
- Excessive intake of **Vitamin A** can lead to **hypervitaminosis A**, causing symptoms like dry skin, headache, liver damage, and bone pain.
- It is not directly linked to the formation of **calcium oxalate stones** or the bipyramidal crystal shape seen here.
*Vitamin E*
- High doses of **Vitamin E** are generally well-tolerated, but very high intake has been linked to increased bleeding risk and gastrointestinal distress.
- There is no established direct link between **Vitamin E supplementation** and the formation of **calcium oxalate kidney stones**.
*Uric acid*
- While the patient has a history of **gout** (which involves uric acid), the presence of **bipyramidal, envelope-shaped crystals** in the urine is specific for **calcium oxalate**, not uric acid.
- **Uric acid stones** typically appear as pleiomorphic, rhomboid, or barrel-shaped crystals and are not radiopaque on routine CT unless mixed with calcium.
Question 180: A 1-year-old boy is brought to his pediatrician for a follow-up appointment. He was recently diagnosed with failure to thrive and developmental delay. His weight is 7 kg (15.4 lb), height is 61 cm (24 in), and head circumference is 42 cm (16.5 in). The patient’s father had a younger sister who suffered from mental and physical delay and died at a very young age. The patient was able to raise his head at the age of 7 months and began to sit alone only recently. He babbles, coos, and smiles to other people. On presentation, his blood pressure is 75/40 mm Hg, heart rate is 147/min, respiratory rate is 28/min, and temperature is 36.4°C (97.5°F). He has a coarse face with small deep orbits, proptotic eyes, big lips, and gingival hyperplasia. His skin is pale with decreased elasticity. His lung and heart sounds are normal. Abdominal examination reveals diminished anterior abdominal wall muscle tone and hepatomegaly. Muscle tone is increased in all groups of muscles on both upper and lower extremities. The physician becomes concerned and performs testing for the suspected hereditary disease. A blood test shows increased lysosomal enzyme concentration in the serum and decreased N-acetylglucosamine-1-phosphotransferase (GlcNAc phosphotransferase) activity within the leukocytes. Which of the statements listed below describes the mechanism of the patient’s condition?
A. The lysosomal enzymes are secreted from the cells instead of being targeted to lysosomes because of lack of mannose phosphorylation on N-linked glycoproteins. (Correct Answer)
B. There is impaired hydrolysis of GM2-ganglioside, which accumulates in the cytoplasm.
C. Due to enzyme deficiency, glycogen is extensively accumulated within the hepatocytes.
D. The patient’s symptoms are due to dysfunctional metabolism of sphingomyelin, which accumulates within the lysosomes.
E. The symptoms result from defective glycolysis, which results in a total energy deficiency.
Explanation: ***The lysosomal enzymes are secreted from the cells instead of being targeted to lysosomes because of lack of mannose phosphorylation on N-linked glycoproteins.***
- This describes **I-cell disease (mucolipidosis II)**, a lysosomal storage disorder characterized by a deficiency of **N-acetylglucosamine-1-phosphotransferase**.
- Without this enzyme, mannose residues on lysosomal enzymes cannot be phosphorylated, preventing their proper targeting to lysosomes and leading to their secretion into the bloodstream.
*There is impaired hydrolysis of GM2-ganglioside, which accumulates in the cytoplasm.*
- This mechanism describes **Tay-Sachs disease**, which is caused by a deficiency in B-hexosaminidase A.
- While Tay-Sachs also causes developmental delay, the clinical features and biochemical findings (specifically the lysosomal enzyme activity levels in serum and leukocytes) do not match those of the described patient.
*Due to enzyme deficiency, glycogen is extensively accumulated within the hepatocytes.*
- This mechanism describes **glycogen storage diseases**, such as Von Gierke disease (type I) or Pompe disease (type II).
- While Pompe disease is a lysosomal storage disorder, the enzymatic defect involves **acid alpha-glucosidase** and leads to glycogen accumulation primarily in muscles and heart, not related to N-acetylglucosamine-1-phosphotransferase deficiency.
*The patient’s symptoms are due to dysfunctional metabolism of sphingomyelin, which accumulates within the lysosomes.*
- This mechanism describes **Niemann-Pick disease**, caused by a deficiency in **sphingomyelinase**.
- While it is a lysosomal storage disease with hepatosplenomegaly and developmental delay, the specific enzymatic defect and the coarse facial features do not align with the patient's presentation and lab results.
*The symptoms result from defective glycolysis, which results in a total energy deficiency.*
- Defective glycolysis would lead to issues with cellular energy production, causing symptoms such as muscle weakness and fatigue.
- However, this mechanism does not explain the specific clinical features like coarse facies, gingival hyperplasia, hepatomegaly, or the characteristic enzymatic defect seen in I-cell disease.
