A 4-month-old boy is brought to the emergency department by his mother because of lethargy and vomiting since he woke up 1 hour ago. The mother says that he last breastfed the previous evening and slept through the night for the first time. His family recently immigrated from Bolivia. His temperature is 38.7°C (101.2°F). Physical examination shows dry mucous membranes and enlarged, reddened tonsils. Serum studies show:
Glucose 42 mg/dL
Ketones 0.2 mg/dL N = < 1 mg/dL
AST 40 U/L
ALT 60 U/L
Ammonia 80 μ/dL (N=15–45)
Which of the following enzymes is most likely deficient in this patient?
Q72
A 24-year-old man presents for an annual check-up. He is a bodybuilder and tells you he is on a protein-rich diet that only allows for minimal carbohydrate intake. His friend suggests he try exogenous glucagon to help him lose some excess weight before an upcoming competition. Which of the following effects of glucagon is he attempting to exploit?
Q73
At postpartum physical examination, a newborn is found to have male external genitalia. Scrotal examination shows a single palpable testicle in the right hemiscrotum. Ultrasound of the abdomen and pelvis shows an undescended left testis, seminal vesicles, uterus, and fallopian tubes. Chromosomal analysis shows a 46, XY karyotype. Which of the following sets of changes is most likely to be found in this newborn?
Legend: Normal = normal levels, ↑ = increased levels, ↓ = decreased levels
SRY-gene activity | Müllerian inhibitory factor (MIF) | Testosterone | Dihydrotestosterone (DHT)
Q74
A 24-year-old woman presents to the emergency department with abdominal pain that started while she was at the gym. The patient competes as a power lifter and states that her pain started after one of her heavier lifts. The patient has no significant past medical history and is currently taking a multivitamin and oral contraceptive pills. She smokes cigarettes and drinks alcohol regularly and is currently sexually active with multiple partners. Her temperature is 99°F (37.2°C), blood pressure is 85/55 mmHg, pulse is 125/min, respirations are 18/min, and oxygen saturation is 99% on room air. Physical exam is notable for right upper quadrant abdominal tenderness, acne, and muscle hypertrophy. Right upper quadrant ultrasound demonstrates a solitary heterogeneous mass. Which of the following other findings is most likely to be found in this patient?
Q75
A 4-year-old boy is brought to the physician because of frequent falls, worsening muscle pain, and poor vision in low light conditions. His mother reports that he has been on a low-fat diet since infancy because of persistent diarrhea. He is at the 5th percentile for height and weight. Physical examination shows bilateral proximal muscle weakness and a wide ataxic gait. His serum cholesterol level is 21 mg/dL. Peripheral blood smear shows red blood cells with irregular spiny projections of varying size. Further evaluation of this patient is most likely to show which of the following findings?
Q76
A 70-year-old chronic smoker presents to the emergency department with a sudden onset of left-sided weakness. The past medical history is insignificant except for hypertension, for which he has been taking medications regularly. The vital signs include: blood pressure 165/110 mm Hg, pulse rate 78/min, respiratory rate 18/min, and temperature 36.1°C (97°F). The neurologic examination shows ⅗ muscle strength in the left upper and lower limbs. An occlusion of a branch of the right middle cerebral artery is suspected because the CT fails to show signs of hemorrhage. The HbA1C is 11%. Which of the following blood lipid components is the most important contributing factor leading to his condition?
Q77
A 16-year-old girl with celiac disease is brought to the physician because of a 1-week history of generalized weakness and tingling around her mouth and in her fingertips. She also complains of abdominal cramps and nausea. In addition to following a gluten-free diet, she has been following a vegan diet for the past 2 years. Physical examination shows involuntary contractions of the muscle at the corner of her mouth and nose that are elicited by tapping on her right cheek. Her parathyroid hormone concentration is 834 pg/mL. Which of the following is the most likely underlying cause for this patient's current condition?
Q78
A 6-month-old infant male is brought to the emergency department with a 1-hour history of vomiting and convulsions. He was born at home and had sporadic prenatal care though his parents say that he appeared healthy at birth. He initially fed well; however, his parents have noticed that he has been feeding poorly and is very irritable since they moved on to baby foods. They have also noticed mild yellowing of his skin but assumed it would go away over time. On presentation, he is found to be very sleepy, and physical exam reveals an enlarged liver and spleen. The rest of the physical exam is normal. Which of the following enzymes is most likely functioning abnormally in this patient?
Q79
A 14-year-old male of eastern European descent presents to the free clinic at a university hospital for a respiratory infection, which his mother explains occurs quite frequently. The male is noted to be of short stature, have a gargoyle-like facies, clouded corneas, poor dentition, and is severely mentally retarded. A urinalysis revealed large amounts of heparan and dermatan sulfate. Which of the following is the most likely diagnosis?
Q80
An autopsy was performed on a 2-year-old male child. The clinical report stated that the child's parents were first cousins, and that he had deteriorated physically and mentally over the past year, becoming deaf, unable to eat, and paralyzed. A brain biopsy demonstrated the accumulation of GM2-gangliosides in the neurons. Which of the following enzymes was missing from this child?
Lipid metabolism US Medical PG Practice Questions and MCQs
Question 71: A 4-month-old boy is brought to the emergency department by his mother because of lethargy and vomiting since he woke up 1 hour ago. The mother says that he last breastfed the previous evening and slept through the night for the first time. His family recently immigrated from Bolivia. His temperature is 38.7°C (101.2°F). Physical examination shows dry mucous membranes and enlarged, reddened tonsils. Serum studies show:
Glucose 42 mg/dL
Ketones 0.2 mg/dL N = < 1 mg/dL
AST 40 U/L
ALT 60 U/L
Ammonia 80 μ/dL (N=15–45)
Which of the following enzymes is most likely deficient in this patient?
A. Galactose-1-phosphate uridyltransferase
B. Medium-chain acyl-CoA dehydrogenase (Correct Answer)
C. Alpha-L-iduronidase
D. Propionyl-CoA carboxylase
E. Lysosomal acid α-1,4- glucosidase
Explanation: ***Medium-chain acyl-CoA dehydrogenase***
- The patient presents with **hypoglycemia** (glucose 42 mg/dL) and **hypoketonemia** (ketone 0.2 mg/dL) after a prolonged fast, which are classic signs of a **fatty acid oxidation disorder**.
- **Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency** leads to impaired breakdown of medium-chain fatty acids, crucial for energy production during fasting, resulting in symptoms like **lethargy**, **vomiting**, and **metabolic derangements**.
*Galactose-1-phosphate uridyltransferase*
- Deficiency of this enzyme causes **classic galactosemia**, presenting with **vomiting**, **jaundice**, **hepatomegaly**, and **cataracts** upon introduction of lactose in the diet.
- While vomiting is present, the key features like jaundice and cataracts are absent, and the primary metabolic issue is not related to glucose and ketone levels in the context of fasting.
*Alpha-L-iduronidase*
- This enzyme deficiency causes **Hurler syndrome (MPS I)**, a lysosomal storage disease characterized by **coarse facial features**, **skeletal abnormalities**, **hepatosplenomegaly**, and **developmental delay**.
- The patient's acute presentation with hypoglycemia and hypoketonemia does not align with the typical long-term, progressive features of a mucopolysaccharidosis.
*Propionyl-CoA carboxylase*
- Deficiency of this enzyme leads to **propionic acidemia**, a type of **organic acidemia**, typically presenting with **ketoacidosis** (elevated ketones), metabolic acidosis, hyperammonemia, and neurological symptoms like seizures and lethargy.
- The patient's **hypoketonemia** is the key distinguishing feature that rules this out; propionic acidemia presents with elevated ketones, not reduced ketones as seen in fatty acid oxidation disorders.
*Lysosomal acid α-1,4-glucosidase*
- Deficiency of this enzyme causes **Pompe disease (glycogen storage disease type II)**, which leads to accumulation of glycogen primarily in muscle and liver, resulting in **cardiomyopathy**, **hypotonia**, and **hepatomegaly**.
- While it is a metabolic disorder, the clinical picture of severe hypoglycemia and hypoketonemia after fasting is not the hallmark of Pompe disease; instead, muscle weakness and cardiac issues dominate.
Question 72: A 24-year-old man presents for an annual check-up. He is a bodybuilder and tells you he is on a protein-rich diet that only allows for minimal carbohydrate intake. His friend suggests he try exogenous glucagon to help him lose some excess weight before an upcoming competition. Which of the following effects of glucagon is he attempting to exploit?
A. Increased glucose utilization by tissues
B. Decreased blood cholesterol level
C. Increased hepatic gluconeogenesis
D. Increased lipolysis in adipose tissues (Correct Answer)
E. Increased hepatic glycogenolysis
Explanation: ***Increased lipolysis in adipose tissues***
- While **glucagon's primary target is the liver**, it can have **modest lipolytic effects** on adipose tissue by opposing insulin's anti-lipolytic actions.
- Glucagon stimulates cAMP production, which can activate **hormone-sensitive lipase** to break down triglycerides into **fatty acids** and **glycerol**.
- However, **catecholamines (epinephrine/norepinephrine)** are far more potent direct stimulators of adipose tissue lipolysis than glucagon.
- The friend is attempting to exploit this lipolytic effect for fat loss, though **exogenous glucagon is not an evidence-based or safe weight-loss strategy**.
*Increased glucose utilization by tissues*
- This is **opposite** to glucagon's actual effect. **Glucagon raises blood glucose** levels; it does not promote glucose uptake by peripheral tissues.
- **Insulin** is the hormone responsible for promoting glucose uptake and utilization by muscle, adipose, and other tissues.
*Decreased blood cholesterol level*
- Glucagon does not have a direct, clinically significant effect on reducing blood cholesterol levels.
- While glucagon affects overall lipid metabolism through its catabolic actions, it is not used therapeutically for hypercholesterolemia.
*Increased hepatic gluconeogenesis*
- **Glucagon strongly stimulates hepatic gluconeogenesis**, which is the synthesis of glucose from non-carbohydrate precursors (amino acids, lactate, glycerol) in the liver.
- This action **raises blood glucose** levels and would not directly contribute to fat loss or weight reduction.
- In the context of a low-carbohydrate diet, increased gluconeogenesis would maintain blood glucose but not promote the fat loss the bodybuilder seeks.
*Increased hepatic glycogenolysis*
- **Glucagon is a potent stimulator of hepatic glycogenolysis**, the breakdown of stored liver glycogen into glucose.
- This rapidly increases blood glucose levels during fasting or hypoglycemia.
- However, this does not directly target adipose tissue for fat loss; it mobilizes glucose stores rather than fat stores, so it's not the mechanism relevant to weight loss goals.
Question 73: At postpartum physical examination, a newborn is found to have male external genitalia. Scrotal examination shows a single palpable testicle in the right hemiscrotum. Ultrasound of the abdomen and pelvis shows an undescended left testis, seminal vesicles, uterus, and fallopian tubes. Chromosomal analysis shows a 46, XY karyotype. Which of the following sets of changes is most likely to be found in this newborn?
Legend: Normal = normal levels, ↑ = increased levels, ↓ = decreased levels
SRY-gene activity | Müllerian inhibitory factor (MIF) | Testosterone | Dihydrotestosterone (DHT)
A. Normal normal normal ↓
B. ↓ ↓ ↓ ↓
C. Normal ↓ normal normal (Correct Answer)
D. ↓ ↓ normal normal
E. Normal normal ↑ ↑
Explanation: ***Normal ↓ Normal Normal***
- A 46, XY karyotype with male external genitalia indicates **normal SRY-gene activity** and normal **testosterone** production, as these are critical for male sexual differentiation.
- The presence of a **uterus and fallopian tubes** in a 46, XY individual is characteristic of persistent **Müllerian duct syndrome**, caused by a **deficiency or insensitivity to Müllerian Inhibiting Factor (MIF)**, leading to a decreased level of MIF.
*Normal Normal Normal ↓*
- This pattern would suggest normal initial male differentiation but an issue downstream, possibly with **5-alpha-reductase deficiency** (leading to decreased DHT) and normal MIF, which would prevent Müllerian structure development.
- The presence of a **uterus and fallopian tubes** contradicts normal MIF levels.
*↓ ↓ ↓ ↓*
- This combination indicates severe defects in all aspects of male sexual development, which would lead to **female external genitalia** or ambiguous genitalia, not male external genitalia.
- Such low levels would also prevent the formation of a palpable testis, and a 46, XY karyotype with female internal structures due to low testosterone and MIF would be highly unlikely to produce male external genitalia.
*↓ ↓ Normal Normal*
- While low MIF would explain the presence of a uterus and fallopian tubes, a **decreased SRY-gene activity** would prevent the development of testes and lead to ambiguous or female external genitalia, rather than male external genitalia.
- Normal testosterone and DHT with decreased SRY gene activity is a contradictory combination, as testosterone production is dependent on the presence of testes.
*Normal Normal ↑ ↑*
- This profile would result in normal male internal and external genitalia, without the presence of **uterus or fallopian tubes**.
- Increased levels of androgens are typically found in conditions like **congenital adrenal hyperplasia** in XX individuals, leading to virilization, but are not consistent with the internal structures seen here.
Question 74: A 24-year-old woman presents to the emergency department with abdominal pain that started while she was at the gym. The patient competes as a power lifter and states that her pain started after one of her heavier lifts. The patient has no significant past medical history and is currently taking a multivitamin and oral contraceptive pills. She smokes cigarettes and drinks alcohol regularly and is currently sexually active with multiple partners. Her temperature is 99°F (37.2°C), blood pressure is 85/55 mmHg, pulse is 125/min, respirations are 18/min, and oxygen saturation is 99% on room air. Physical exam is notable for right upper quadrant abdominal tenderness, acne, and muscle hypertrophy. Right upper quadrant ultrasound demonstrates a solitary heterogeneous mass. Which of the following other findings is most likely to be found in this patient?
A. Elevated viral core antigen
B. Elevated alpha fetoprotein
C. Increased pigmentation in flexural areas
D. Prolonged PT and PTT
E. Increased LDL and decreased HDL (Correct Answer)
Explanation: ***Increased LDL and decreased HDL***
- This patient's presentation is most consistent with **hepatic adenoma rupture** related to **anabolic steroid use** (suggested by powerlifting, muscle hypertrophy, and acne) combined with oral contraceptive use.
- **Anabolic steroids have well-documented effects on lipid metabolism**, characteristically causing **decreased HDL cholesterol** and **increased LDL cholesterol**, which significantly increases cardiovascular risk.
- This lipid pattern is one of the most consistent and clinically significant metabolic effects of anabolic steroid abuse and would be expected in this patient.
*Elevated alpha fetoprotein*
- **Alpha-fetoprotein (AFP)** is a tumor marker for **hepatocellular carcinoma (HCC)**, not hepatic adenoma.
- While anabolic steroids can cause hepatic adenomas and rarely HCC, this acute presentation with hemodynamic instability in a young woman on oral contraceptives is classic for **ruptured hepatic adenoma**, which does **not** elevate AFP.
- AFP elevation would not be expected in this clinical scenario.
*Elevated viral core antigen*
- Elevated viral core antigen would indicate active **hepatitis B infection**, a risk factor for chronic liver disease and HCC.
- There is no evidence in this vignette to suggest viral hepatitis, and this would not be related to the acute presentation or anabolic steroid use.
*Increased pigmentation in flexural areas*
- **Acanthosis nigricans** (hyperpigmentation in flexural areas) is associated with insulin resistance and certain malignancies.
- While anabolic steroids can affect glucose metabolism, acanthosis nigricans is not a characteristic finding of steroid use or hepatic adenoma.
*Prolonged PT and PTT*
- While severe liver dysfunction can cause coagulopathy with prolonged PT and PTT, this is not the most characteristic finding in hepatic adenoma.
- The acute presentation is more likely due to hemorrhage from adenoma rupture rather than chronic liver failure with synthetic dysfunction.
Question 75: A 4-year-old boy is brought to the physician because of frequent falls, worsening muscle pain, and poor vision in low light conditions. His mother reports that he has been on a low-fat diet since infancy because of persistent diarrhea. He is at the 5th percentile for height and weight. Physical examination shows bilateral proximal muscle weakness and a wide ataxic gait. His serum cholesterol level is 21 mg/dL. Peripheral blood smear shows red blood cells with irregular spiny projections of varying size. Further evaluation of this patient is most likely to show which of the following findings?
A. Post-prandial lipid-laden enterocytes (Correct Answer)
B. IgA anti-tissue transglutaminase antibodies
C. Sweat chloride levels > 60 mmol/L
D. Fibrofatty replacement of muscle tissue
E. GAA trinucleotide repeats on chromosome 9
Explanation: ***Post-prandial lipid-laden enterocytes***
- This finding would be characteristic of **abetalipoproteinemia** due to the inability to properly form and secrete **chylomicrons** from enterocytes.
- The clinical picture of **malabsorption**, **neurological symptoms** (ataxia, muscle weakness), **retinopathy** (poor night vision), **low serum cholesterol**, and **acanthocytosis** (spiny red blood cells) is highly suggestive of abetalipoproteinemia.
*IgA anti-tissue transglutaminase antibodies*
- These antibodies are characteristic of **celiac disease**, which involves an immune reaction to gluten causing intestinal damage.
- While celiac disease causes malabsorption, it does not explain the **neurological symptoms**, **retinopathy**, or **acanthocytosis** seen in this patient.
*Sweat chloride levels > 60 mmol/L*
- Elevated sweat chloride levels are the diagnostic hallmark of **cystic fibrosis**.
- While cystic fibrosis can cause malabsorption and growth failure due to pancreatic insufficiency, it does not typically lead to the described **neurological manifestations**, **retinopathy**, or **acanthocytosis**.
*Fibrofatty replacement of muscle tissue*
- This is a characteristic finding in muscular dystrophies, such as **Duchenne muscular dystrophy**, where muscle tissue is progressively replaced by fat and fibrous connective tissue.
- However, muscular dystrophy does not explain the **malabsorption**, **retinopathy**, **low cholesterol**, or **acanthocytosis** observed in this patient.
*GAA trinucleotide repeats on chromosome 9*
- This genetic abnormality is associated with **Friedreich's ataxia**, a hereditary neurodegenerative disorder.
- While Friedreich's ataxia causes **ataxia** and neurological symptoms, it does not typically present with **malabsorption**, **retinopathy**, or **acanthocytosis** in the way described in this case, particularly with the very low cholesterol level.
Question 76: A 70-year-old chronic smoker presents to the emergency department with a sudden onset of left-sided weakness. The past medical history is insignificant except for hypertension, for which he has been taking medications regularly. The vital signs include: blood pressure 165/110 mm Hg, pulse rate 78/min, respiratory rate 18/min, and temperature 36.1°C (97°F). The neurologic examination shows ⅗ muscle strength in the left upper and lower limbs. An occlusion of a branch of the right middle cerebral artery is suspected because the CT fails to show signs of hemorrhage. The HbA1C is 11%. Which of the following blood lipid components is the most important contributing factor leading to his condition?
A. Lipoprotein lipase (LPL) deficiency
B. Very low-density lipoprotein (VLDL)
C. Chylomicron
D. High-density lipoprotein (HDL)-cholesterol
E. Oxidized low-density lipoprotein (ox-LDL) (Correct Answer)
Explanation: ***Oxidized low-density lipoprotein (ox-LDL)***
- The patient has multiple risk factors for **atherosclerosis**, including **hypertension**, **smoking**, and **poorly controlled diabetes (HbA1c 11%)**.
- **Oxidized LDL** is a key player in atherogenesis; it promotes endothelial dysfunction, foam cell formation, and plaque buildup, ultimately leading to arterial occlusion and stroke.
*Lipoprotein lipase (LPL) deficiency*
- LPL deficiency primarily causes **severe hypertriglyceridemia** and can lead to recurrent pancreatitis.
- While hypertriglyceridemia is a risk factor for cardiovascular disease, LPL deficiency itself is not the most direct or potent contributor to the atherosclerotic process leading to an ischemic stroke in this context.
*Very low-density lipoprotein (VLDL)*
- VLDL transports triglycerides and is a precursor to LDL, contributing to atherogenesis.
- However, **oxidized LDL** is considered a more direct and potent pro-atherogenic particle in the development of plaques that lead to ischemic stroke.
*Chylomicron*
- Chylomicrons are responsible for transporting dietary fats from the intestines and are typically cleared rapidly from the blood.
- Elevated chylomicrons are primarily associated with **severe hypertriglyceridemia** and pancreatitis, rather than a direct and significant contribution to atherosclerotic stroke.
*High-density lipoprotein (HDL)-cholesterol*
- **HDL-cholesterol** is generally considered protective against atherosclerosis due to its role in reverse cholesterol transport.
- Low levels of HDL are a risk factor, but high HDL itself does not cause ischemic stroke; instead, it is often associated with a reduced risk.
Question 77: A 16-year-old girl with celiac disease is brought to the physician because of a 1-week history of generalized weakness and tingling around her mouth and in her fingertips. She also complains of abdominal cramps and nausea. In addition to following a gluten-free diet, she has been following a vegan diet for the past 2 years. Physical examination shows involuntary contractions of the muscle at the corner of her mouth and nose that are elicited by tapping on her right cheek. Her parathyroid hormone concentration is 834 pg/mL. Which of the following is the most likely underlying cause for this patient's current condition?
A. Autoimmune-mediated destruction of parathyroid tissue
B. Decreased levels of renal 1α-hydroxylase
C. Decreased conversion of 7-dehydrocholesterol to cholecalciferol
D. Decreased intestinal absorption of ergocalciferol (Correct Answer)
E. Decreased dietary intake of ergocalciferol
Explanation: ***Decreased intestinal absorption of ergocalciferol***
- The patient's symptoms of **generalized weakness, perioral and fingertip tingling, abdominal cramps, and Chvostek's sign** (involuntary muscle contractions on facial tapping) are classic manifestations of **hypocalcemia**. Her high **parathyroid hormone (PTH)** concentration (834 pg/mL, normal range 10-65 pg/mL) indicates **secondary hyperparathyroidism**, a compensatory response to hypocalcemia.
- Given her history of **celiac disease** and **veganism**, she has multiple risk factors for **vitamin D malabsorption**. Celiac disease causes **malabsorption** of fat-soluble vitamins (A, D, E, K) due to damage to the small intestinal villi. **Ergocalciferol (vitamin D2)** is a form of vitamin D found in plant foods and supplements, and its absorption would be compromised in both states. Impaired vitamin D absorption leads to decreased calcium absorption, triggering secondary hyperparathyroidism.
*Autoimmune-mediated destruction of parathyroid tissue*
- This scenario describes **primary hypoparathyroidism**, which would lead to **low PTH levels**, not the elevated PTH observed in the patient.
- While it causes hypocalcemia, the underlying pathology and hormonal profile are inconsistent with the patient's presentation.
*Decreased levels of renal 1α-hydroxylase*
- This enzyme is crucial for converting 25-hydroxyvitamin D to its active form, **1,25-dihydroxyvitamin D (calcitriol)**, in the kidneys. Decreased levels are a hallmark of **chronic kidney disease**.
- While it leads to hypocalcemia, the patient's history does not suggest kidney disease, and primary issues with intestinal absorption are more likely given her celiac disease.
*Decreased conversion of 7-dehydrocholesterol to cholecalciferol*
- This conversion occurs in the skin upon exposure to **UVB light** and is the primary natural source of **cholecalciferol (vitamin D3)**.
- While lack of sun exposure can cause vitamin D deficiency, it doesn't directly explain the malabsorption issues related to her **celiac disease**, which would affect dietary vitamin D forms.
*Decreased dietary intake of ergocalciferol*
- While a **vegan diet** can be deficient in certain nutrients, including vitamin D, the primary issue is likely **malabsorption** due to **celiac disease**.
- A simple dietary deficiency alone wouldn't explain such severe hypocalcemia with high PTH in a 16-year-old, especially when coupled with intestinal pathology.
Question 78: A 6-month-old infant male is brought to the emergency department with a 1-hour history of vomiting and convulsions. He was born at home and had sporadic prenatal care though his parents say that he appeared healthy at birth. He initially fed well; however, his parents have noticed that he has been feeding poorly and is very irritable since they moved on to baby foods. They have also noticed mild yellowing of his skin but assumed it would go away over time. On presentation, he is found to be very sleepy, and physical exam reveals an enlarged liver and spleen. The rest of the physical exam is normal. Which of the following enzymes is most likely functioning abnormally in this patient?
A. Aldolase B (Correct Answer)
B. Galactokinase
C. Lactase
D. Fructokinase
E. Gal-1-phosphate uridyl transferase
Explanation: ***Aldolase B***
- The symptoms of vomiting, irritability, jaundice, hepatosplenomegaly, and poor feeding in an infant after starting baby foods strongly suggest **hereditary fructose intolerance (HFI)**.
- HFI is caused by a deficiency in **Aldolase B**, which is responsible for cleaving **fructose-1-phosphate** into dihydroxyacetone phosphate and glyceraldehyde in the liver, kidney, and small intestine.
*Galactokinase*
- A deficiency in **galactokinase** causes **galactosemia type II**, characterized primarily by **cataracts** from birth, with milder symptoms compared to classic galactosemia.
- It does not typically present with the severe liver failure, vomiting, and convulsions seen in this patient.
*Lactase*
- **Lactase deficiency** causes **lactose intolerance**, presenting with gastrointestinal symptoms like bloating, gas, and diarrhea, particularly after consuming milk products.
- It does not typically cause the systemic symptoms of liver dysfunction, vomiting, convulsions, or jaundice experienced by this infant.
*Fructokinase*
- A deficiency in **fructokinase** causes **essential fructosuria**, which is a **benign, asymptomatic** metabolic disorder.
- Fructose accumulates in the urine but does not lead to the severe clinical manifestations such as vomiting, convulsions, or liver enlargement.
*Gal-1-phosphate uridyl transferase*
- A deficiency in **Gal-1-phosphate uridyl transferase** causes **classic galactosemia**, which would also present with vomiting, feeding difficulties, jaundice, and hepatosplenomegaly.
- However, classic galactosemia symptoms appear upon ingestion of **lactose** (from breast milk or formula), typically much earlier than the introduction of baby foods containing fructose.
Question 79: A 14-year-old male of eastern European descent presents to the free clinic at a university hospital for a respiratory infection, which his mother explains occurs quite frequently. The male is noted to be of short stature, have a gargoyle-like facies, clouded corneas, poor dentition, and is severely mentally retarded. A urinalysis revealed large amounts of heparan and dermatan sulfate. Which of the following is the most likely diagnosis?
A. Hurler's syndrome (Correct Answer)
B. Gaucher's disease
C. Hunter's syndrome
D. Fabry's disease
E. Tay Sachs disease
Explanation: ***Hurler's syndrome***
- This patient presents with classic features of Hurler's syndrome, including **short stature**, **gargoyle-like facies**, **clouded corneas**, poor dentition, and **severe mental retardation**.
- The finding of **heparan and dermatan sulfate** in the urine is diagnostic, indicating a deficiency in the enzyme **alpha-L-iduronidase**, which leads to the accumulation of these **glycosaminoglycans (GAGs)**.
*Gaucher's disease*
- Characterized by **hepatosplenomegaly**, **bone crises**, and **pancytopenia** due to glucocerebroside accumulation.
- It does not typically cause **clouded corneas** or the specific facial dysmorphia described.
*Hunter's syndrome*
- While similar to Hurler's in some ways (also involves GAG accumulation), Hunter's syndrome is **X-linked recessive**, and a key differentiating feature is the **absence of corneal clouding**.
- The deficient enzyme is **iduronate sulfatase**, and it also presents with characteristic facial features and mental retardation.
*Fabry's disease*
- This is an **X-linked lysosomal storage disease** characterized by **angiokeratomas**, **neuropathic pain**, **renal failure**, and **corneal opacities** (verticillata), but not the severe skeletal and facial dysmorphia seen in this patient.
- It involves the accumulation of globotriaosylceramide due to deficiency of **alpha-galactosidase A**.
*Tay Sachs disease*
- Primarily a neurological disorder characterized by **progressive neurodegeneration**, **developmental delay**, **blindness**, and a **cherry-red spot** on the retina.
- It does not involve skeletal deformities, coarse facial features, or corneal clouding, and accumulation is of GM2 gangliosides due to **hexosaminidase A** deficiency.
Question 80: An autopsy was performed on a 2-year-old male child. The clinical report stated that the child's parents were first cousins, and that he had deteriorated physically and mentally over the past year, becoming deaf, unable to eat, and paralyzed. A brain biopsy demonstrated the accumulation of GM2-gangliosides in the neurons. Which of the following enzymes was missing from this child?
A. Sphingomyelinase
B. Hexosaminidase A (Correct Answer)
C. α-galactosidase A
D. β-galactocerebrosidase
E. α-L-iduronidase
Explanation: ***Hexosaminidase A***
- The accumulation of **GM2-gangliosides** in neurons, coupled with severe neurological decline (deafness, paralysis, mental and physical deterioration), is characteristic of **Tay-Sachs disease**.
- **Tay-Sachs disease** is caused by a deficiency of the enzyme **hexosaminidase A**, which is responsible for the breakdown of GM2-gangliosides.
*α-L-iduronidase*
- A deficiency in **α-L-iduronidase** causes **Hurler syndrome (MPS I)**, which involves the accumulation of heparan sulfate and dermatan sulfate.
- While Hurler syndrome involves severe developmental delay and coarse facial features, it does not typically present with the specific GM2-ganglioside accumulation seen here.
*α-galactosidase A*
- A deficiency in **α-galactosidase A** causes **Fabry disease**, leading to the accumulation of globotriaosylceramide (Gb3).
- Symptoms of Fabry disease include neuropathic pain, angiokeratomas, and renal/cardiac complications, which differ from this child's presentation.
*Sphingomyelinase*
- A deficiency in **sphingomyelinase** causes **Niemann-Pick disease (Type A and B)**, leading to the accumulation of sphingomyelin.
- Niemann-Pick disease often presents with hepatosplenomegaly, neurodegeneration (Type A), and lung disease, which are not mentioned as primary findings.
*β-galactocerebrosidase*
- A deficiency in **β-galactocerebrosidase** causes **Krabbe disease (globoid cell leukodystrophy)**, leading to the accumulation of galactocerebroside.
- Krabbe disease causes severe neurological deterioration, but the hallmark is the presence of **globoid cells** and **demyelination**, not GM2-ganglioside accumulation.
