Clinical manifestations by tissue involvement — MCQs

10 questions

A 15-year-old boy is sent from gym class with a chief complaint of severe muscle aches. In class today he was competing with his friends and therefore engaged in weightlifting for the first time. A few hours later he was extremely sore and found that his urine was red when he went to urinate. This concerned him and he was sent to the emergency department for evaluation. Upon further questioning, you learn that since childhood he has always had muscle cramps with exercise. Physical exam was unremarkable. Upon testing, his creatine kinase level was elevated and his urinalysis was negative for blood and positive for myoglobin. Thinking back to biochemistry you suspect that he may be suffering from a hereditary glycogen disorder. Given this suspicion, what would you expect to find upon examination of his cells?

A 3-month-old girl is brought to the emergency department by her parents after she appeared to have a seizure at home. On presentation, she no longer has convulsions though she is still noted to be lethargic. She was born through uncomplicated vaginal delivery and was not noted to have any abnormalities at the time of birth. Since then, she has been noted by her pediatrician to be falling behind in height and weight compared to similarly aged infants. Physical exam reveals an enlarged liver, and laboratory tests reveal a glucose of 38 mg/dL. Advanced testing shows that a storage molecule present in the cells of this patient has abnormally short outer chains. Which of the following enzymes is most likely defective in this patient?

A 5-month-old boy presents with increasing weakness for the past 3 months. The patient’s mother says that the weakness is accompanied by dizziness, sweating, and vertigo early in the morning. Physical examination shows hepatomegaly. Laboratory findings show an increased amount of lactate, uric acid, and elevated triglyceride levels. Which of the following enzymes is most likely deficient in this patient?

A 2-month-old boy is brought to the emergency department 25 minutes after having a seizure. He has had multiple seizures during the past week. His mother has noticed that he has become lethargic and has had a weak cry for the past month. He was born at 37 weeks' gestation. He is at the 20th percentile for height and 15th percentile for weight. His temperature is 36.7°C (98°F), respirations are 50/min, and pulse is 140/min. Examination shows a soft and nontender abdomen. The liver is palpated 4 cm below the right costal margin; there is no splenomegaly. Serum studies show: Na+ 137 mEq/L Cl- 103 mEq/L K+ 3.9 mEq/L Glucose 32 mg/dL Calcium 9.6 mg/dL Total cholesterol 202 mg/dL Triglycerides 260 mg/dL Lactate 4.2 mEq/L (N = 0.5 - 2.2 mEq/L) A deficiency of which of the following enzymes is the most likely cause of this infant's symptoms?

A 9-month-old girl is brought to the physician because of a 1-month history of poor feeding and irritability. She is at the 15th percentile for height and 5th percentile for weight. Examination shows hypotonia and wasting of skeletal muscles. Cardiopulmonary examination shows no abnormalities. There is hepatomegaly. Her serum glucose is 61 mg/dL, creatinine kinase is 100 U/L, and lactic acid is within the reference range. Urine ketone bodies are elevated. Which of the following enzymes is most likely deficient in this patient?

A 28-year-old man is brought in by ambulance to the ER, barely conscious, after feeling drowsy and falling to the floor during a presentation several hours ago. His colleague who accompanied him says he has had similar episodes 5 times in the past 3 months. No significant past medical history. His blood pressure is 110/80 mm Hg and pulse is 114/min. His capillary blood glucose is 15 mg/dL. Immediate IV dextrose with thiamine is started, and he rapidly regains consciousness. A contrast CT of the abdomen is performed which reveals a tumor in the pancreas. Which of the following relative laboratory findings would you most likely expect to find in this patient?

A patient presents to the emergency room in an obtunded state. The patient is a known nurse within the hospital system and has no history of any medical problems. A finger stick blood glucose is drawn showing a blood glucose of 25 mg/dL. The patient's daughter immediately arrives at the hospital stating that her mother has been depressed recently and that she found empty syringes in the bathroom at the mother's home. Which of the following is the test that will likely reveal the diagnosis?

A 6-day-old female newborn is brought to the physician because of yellowish discoloration of her eyes and body, vomiting, and poor feeding for 3 days. She has had diarrhea for the past 2 days. She was born at 38 weeks' gestation and the antenatal period was uncomplicated. She appears lethargic. Vital signs are within normal limits. Examination shows jaundice of the skin and conjunctivae. Bilateral cataracts are present. The abdomen is soft and nontender. The liver is palpated 4-cm below the right costal margin; there is no splenomegaly. Muscle tone is decreased in all extremities. Serum glucose concentration is 37 mg/dL. Which of the following is the most appropriate recommendation to prevent long-term complications of this illness?

A newborn infant presents with severe weakness. He was born to a G1P1 mother at 40 weeks gestation with the pregnancy attended by a midwife. The mother's past medical history is unremarkable. She took a prenatal vitamin and folic acid throughout the pregnancy. Since birth, the child has had trouble breastfeeding despite proper counseling. He also has had poor muscle tone and a weak cry. His temperature is 99.5°F (37.5°C), blood pressure is 57/38 mmHg, pulse is 150/min, respirations are 37/min, and oxygen saturation is 96% on room air. Physical exam reveals poor muscle tone. The patient's sucking reflex is weak, and an enlarged tongue is noted. An ultrasound is performed, and is notable for hypertrophy of the myocardium. Which of the following is the most likely diagnosis?

Q10

A 1-year-old male with a history of recurrent pseudomonal respiratory infections and steatorrhea presents to the pediatrician for a sweat test. The results demonstrate a chloride concentration of 70 mEq/L (nl < 40 mEq/L). Which of the following defects has a similar AUTOSOMAL RECESSIVE mode of inheritance as the disorder experienced by this patient?

Clinical manifestations by tissue involvement US Medical PG Practice Questions and MCQs

Question 1: A 15-year-old boy is sent from gym class with a chief complaint of severe muscle aches. In class today he was competing with his friends and therefore engaged in weightlifting for the first time. A few hours later he was extremely sore and found that his urine was red when he went to urinate. This concerned him and he was sent to the emergency department for evaluation. Upon further questioning, you learn that since childhood he has always had muscle cramps with exercise. Physical exam was unremarkable. Upon testing, his creatine kinase level was elevated and his urinalysis was negative for blood and positive for myoglobin. Thinking back to biochemistry you suspect that he may be suffering from a hereditary glycogen disorder. Given this suspicion, what would you expect to find upon examination of his cells?

A. Normal glycogen structure (Correct Answer)
B. Short outer glycogen chains
C. Accumulation of glycogen in lysosomes forming dense granules
D. Glycogen without normal branching pattern
E. Absence of glycogen in muscles

Explanation: ***Normal glycogen structure*** - The patient's symptoms (exercise-induced muscle cramps, myoglobinuria, and elevated CK) are classic for **McArdle disease** (Glycogen Storage Disease Type V), caused by a deficiency in **muscle glycogen phosphorylase**. - In McArdle disease, the enzyme responsible for breaking down glycogen (glycogen phosphorylase) is deficient, but the enzymes involved in synthesizing glycogen are normal. Therefore, the **structure of glycogen is normal**, but it accumulates in muscle cells because it cannot be catabolized. *Short outer glycogen chains* - **Short outer glycogen chains** are characteristic of **Cori disease** (Glycogen Storage Disease Type III), caused by a deficiency in **debranching enzyme**. - This condition also presents with hypoglycemia and hepatomegaly, which are not described in the patient's presentation. *Accumulation of glycogen in lysosomes forming dense granules* - **Accumulation of glycogen in lysosomes** and the formation of **dense granules** is characteristic of **Pompe disease** (Glycogen Storage Disease Type II), caused by a deficiency in **lysosomal alpha-glucosidase (acid maltase)**. - Pompe disease typically presents as a severe infantile form with cardiomegaly and hypotonia, or a later-onset form with proximal muscle weakness, which differs from the patient's primary complaint of exercise intolerance and myoglobinuria. *Glycogen without normal branching pattern* - **Glycogen without a normal branching pattern** (very long unbranched chains) is characteristic of **Andersen disease** (Glycogen Storage Disease Type IV), caused by a deficiency in **branching enzyme**. - This condition typically leads to cirrhosis and liver failure in infancy, which is not consistent with the patient's presentation. *Absence of glycogen in muscles* - While McArdle disease involves an inability to break down muscle glycogen, it does not result in the **absence of glycogen** in muscles; rather, there is an **over-accumulation** of normal-structured glycogen because it cannot be utilized. - The defect is in **glycogenolysis**, not glycogen synthesis, so glycogen is formed but not broken down.

Question 2: A 3-month-old girl is brought to the emergency department by her parents after she appeared to have a seizure at home. On presentation, she no longer has convulsions though she is still noted to be lethargic. She was born through uncomplicated vaginal delivery and was not noted to have any abnormalities at the time of birth. Since then, she has been noted by her pediatrician to be falling behind in height and weight compared to similarly aged infants. Physical exam reveals an enlarged liver, and laboratory tests reveal a glucose of 38 mg/dL. Advanced testing shows that a storage molecule present in the cells of this patient has abnormally short outer chains. Which of the following enzymes is most likely defective in this patient?

A. Debranching enzyme (Correct Answer)
B. Hepatic phosphorylase
C. Glucose-6-phosphatase
D. Muscle phosphorylase
E. Branching enzyme

Explanation: ***Debranching enzyme*** - The presence of **abnormally short outer chains** in a storage molecule, along with **hypoglycemia** and **hepatomegaly**, strongly suggests a defect in the **debranching enzyme** (Type III Glycogen Storage Disease or Cori/Forbes disease). This enzyme is responsible for breaking down the α-1,6 glycosidic bonds at the branch points of glycogen. - Deficiency leads to the accumulation of glycogen with **short branches**, affecting both liver and muscle. *Hepatic phosphorylase* - A defect in **hepatic phosphorylase** (Type VI Glycogen Storage Disease or Hers' disease) leads to similar symptoms like **hepatomegaly** and **hypoglycemia**. - However, the glycogen structure would be normal, not characterized by abnormally short outer chains. *Glucose-6-phosphatase* - A deficiency in **glucose-6-phosphatase** (Type I Glycogen Storage Disease or Von Gierke's disease) leads to severe **hypoglycemia**, **hepatomegaly**, and often **renal enlargement**. - Glycogen structure in this condition is typically normal, with **increased hepatic glycogen stores**. *Muscle phosphorylase* - A deficiency in **muscle phosphorylase** (Type V Glycogen Storage Disease or McArdle's disease) primarily affects skeletal muscle function, causing **muscle cramping**, pain, and **fatigue during exercise**. - It does not typically present with severe **hypoglycemia** or **hepatomegaly** because the liver enzyme is unaffected. *Branching enzyme* - A defect in the **branching enzyme** (Type IV Glycogen Storage Disease or Andersen's disease) results in glycogen with **abnormally long unbranched chains** and fewer branch points. - This typically leads to **cirrhosis** and liver failure, and while hypoglycemia can occur, the characteristic glycogen structure is the opposite of what is described in the patient.

Question 3: A 5-month-old boy presents with increasing weakness for the past 3 months. The patient’s mother says that the weakness is accompanied by dizziness, sweating, and vertigo early in the morning. Physical examination shows hepatomegaly. Laboratory findings show an increased amount of lactate, uric acid, and elevated triglyceride levels. Which of the following enzymes is most likely deficient in this patient?

A. Hepatic glycogen phosphorylase
B. Debranching enzyme
C. Glucose-6-phosphatase (Correct Answer)
D. Muscle glycogen phosphorylase
E. Lysosomal α-1,4-glucosidase

Explanation: ***Glucose-6-phosphatase*** - The constellation of **hypoglycemia** (weakness, dizziness, sweating, vertigo, especially early morning), **hepatomegaly**, **lactic acidosis**, **hyperuricemia**, and **hypertriglyceridemia** are classic features of **Type I glycogen storage disease (von Gierke disease)**, which is caused by a deficiency of **glucose-6-phosphatase**. - This enzyme is crucial for the final step of both **glycogenolysis** and **gluconeogenesis**, releasing free glucose into the bloodstream; its deficiency leads to an inability to maintain normal blood glucose levels during fasting and accumulation of glucose-6-phosphate, which shunts into other metabolic pathways. *Hepatic glycogen phosphorylase* - Deficiency in **hepatic glycogen phosphorylase** (Type VI glycogen storage disease, Hers disease) would cause **hepatomegaly** and **hypoglycemia**, but typically does not present with severe **lactic acidosis**, **hyperuricemia**, or **hypertriglyceridemia** to the same degree as von Gierke disease. - The primary defect is in breaking down glycogen, leading to its accumulation in the liver, but the products of glycolysis can still exit the liver via gluconeogenesis. *Debranching enzyme* - Deficiency in **debranching enzyme** (Type III glycogen storage disease, Cori or Forbes disease) causes **hepatomegaly** and **hypoglycemia**, but usually presents with milder symptoms and less severe **lactic acidosis**, **hyperuricemia**, and **hypertriglyceridemia**. - Patients often present with symptoms similar to Type I, but muscle involvement is also common, and **glycogen structures with short outer branches** are characteristic. *Muscle glycogen phosphorylase* - Deficiency in **muscle glycogen phosphorylase** (Type V glycogen storage disease, McArdle disease) primarily affects **skeletal muscle**, leading to exercise intolerance, muscle pain, and myoglobinuria. - It does not typically cause **hypoglycemia** or **hepatomegaly**, as the liver enzyme is functional, and the symptoms described are systemic rather than muscle-specific. *Lysosomal α-1,4-glucosidase* - Deficiency in **lysosomal α-1,4-glucosidase** (Type II glycogen storage disease, Pompe disease) primarily affects the **heart, muscle, and liver**, causing severe **cardiomyopathy**, hypotonia, and **hepatomegaly**. - While it involves glycogen accumulation, it typically does not present with **hypoglycemia** (as cytoplasmic glycogen metabolism is intact), **lactic acidosis**, or the specific metabolic derangements seen in this patient.

Question 4: A 2-month-old boy is brought to the emergency department 25 minutes after having a seizure. He has had multiple seizures during the past week. His mother has noticed that he has become lethargic and has had a weak cry for the past month. He was born at 37 weeks' gestation. He is at the 20th percentile for height and 15th percentile for weight. His temperature is 36.7°C (98°F), respirations are 50/min, and pulse is 140/min. Examination shows a soft and nontender abdomen. The liver is palpated 4 cm below the right costal margin; there is no splenomegaly. Serum studies show: Na+ 137 mEq/L Cl- 103 mEq/L K+ 3.9 mEq/L Glucose 32 mg/dL Calcium 9.6 mg/dL Total cholesterol 202 mg/dL Triglycerides 260 mg/dL Lactate 4.2 mEq/L (N = 0.5 - 2.2 mEq/L) A deficiency of which of the following enzymes is the most likely cause of this infant's symptoms?

A. Galactose 1-phosphate uridyltransferase
B. Glycogen branching enzyme
C. Glucose 6-phosphatase (Correct Answer)
D. Fructokinase
E. Acid maltase

Explanation: ***Glucose 6-phosphatase*** - The constellation of **hypoglycemia**, **lactic acidosis**, **hepatomegaly**, and **hyperlipidemia** in an infant is characteristic of **Type I glycogen storage disease (von Gierke's disease)**, which is caused by a deficiency of glucose 6-phosphatase. - Seizures and lethargy are common manifestations of severe hypoglycemia in infants. *Galactose 1-phosphate uridyltransferase* - Deficiency of this enzyme causes **classic galactosemia**, which typically presents with **jaundice**, **cataracts**, **vomiting**, and **failure to thrive**, usually after initiation of milk feeds. - While patients can develop hepatomegaly and hypoglycemia, the prominent lactic acidosis and hyperlipidemia seen here are less typical. *Glycogen branching enzyme* - Deficiency causes **Type IV glycogen storage disease (Andersen's disease)**, characterized by **hepatosplenomegaly**, **failure to thrive**, and progressive cirrhosis. - Hypoglycemia is generally less severe, and lactic acidosis and hyperlipidemia are not primary features in the same way as Type I GSD. *Fructokinase* - Deficiency causes **essential fructosuria**, a benign condition where fructose accumulates in the urine. - It is typically asymptomatic and does not lead to hypoglycemia, lactic acidosis, or hepatomegaly. *Acid maltase* - Deficiency (alpha-1,4-glucosidase) causes **Type II glycogen storage disease (Pompe's disease)**, which primarily affects skeletal and cardiac muscle. - The infantile form presents with **severe hypotonia** ("floppy baby"), **cardiomyopathy**, and **macroglossia**. Hepatomegaly, hypoglycemia, and lactic acidosis are not prominent features.

Question 5: A 9-month-old girl is brought to the physician because of a 1-month history of poor feeding and irritability. She is at the 15th percentile for height and 5th percentile for weight. Examination shows hypotonia and wasting of skeletal muscles. Cardiopulmonary examination shows no abnormalities. There is hepatomegaly. Her serum glucose is 61 mg/dL, creatinine kinase is 100 U/L, and lactic acid is within the reference range. Urine ketone bodies are elevated. Which of the following enzymes is most likely deficient in this patient?

A. Glucose-6-phosphatase
B. Muscle phosphorylase
C. Acid alpha-glucosidase
D. Glycogen debrancher (Correct Answer)
E. Glucocerebrosidase

Explanation: ***Glycogen debrancher*** - The patient's symptoms of **hepatomegaly**, **hypoglycemia**, **poor feeding**, **growth failure**, and **elevated urine ketones** in the presence of normal lactic acid suggest Type III glycogen storage disease (Cori disease), caused by a deficiency in **glycogen debrancher enzyme**. - **Muscle wasting** and **hypotonia** are also consistent with Type III GSD, as the debranching enzyme is present in both liver and muscle. *Glucose-6-phosphatase* - Deficiency in **glucose-6-phosphatase** (Type I GSD, Von Gierke disease) also presents with **hepatomegaly** and **hypoglycemia**. - However, Type I GSD is characterized by **lactic acidosis**, which is explicitly stated as normal in this patient, and **hyperlipidemia**, which is not mentioned. *Muscle phosphorylase* - Deficiency in **muscle phosphorylase** (Type V GSD, McArdle disease) primarily affects skeletal muscle, causing **exercise intolerance** and **muscle pain**. - It does not typically present with **hypoglycemia**, **hepatomegaly**, or **growth failure** in infancy. *Acid alpha-glucosidase* - Deficiency in **acid alpha-glucosidase** (Type II GSD, Pompe disease) causes accumulation of glycogen in lysosomes, leading to severe **cardiomyopathy**, **hypotonia**, and **muscle weakness**. - While hypotonia is present, the absence of **cardiomegaly** and significant **liver involvement** makes this diagnosis less likely. *Glucocerebrosidase* - Deficiency in **glucocerebrosidase** causes Gaucher disease, a lysosomal storage disorder, not a glycogen storage disorder. - Symptoms include **hepatosplenomegaly**, **bone crises**, and neurological symptoms, but not **hypoglycemia** or isolated muscle wasting directly related to glycogen metabolism.

Question 6: A 28-year-old man is brought in by ambulance to the ER, barely conscious, after feeling drowsy and falling to the floor during a presentation several hours ago. His colleague who accompanied him says he has had similar episodes 5 times in the past 3 months. No significant past medical history. His blood pressure is 110/80 mm Hg and pulse is 114/min. His capillary blood glucose is 15 mg/dL. Immediate IV dextrose with thiamine is started, and he rapidly regains consciousness. A contrast CT of the abdomen is performed which reveals a tumor in the pancreas. Which of the following relative laboratory findings would you most likely expect to find in this patient?

A. Glucose: ↑, Insulin: ↓, C-Peptide: ↓, Ketoacidosis: Present
B. Glucose: Normal, Insulin: Normal, C-Peptide: Normal, Ketoacidosis: Absent
C. Glucose: ↓, Insulin: ↑, C-Peptide: ↑, Ketoacidosis: Absent (Correct Answer)
D. Glucose: ↓, Insulin: ↑, C-Peptide: ↓, Ketoacidosis: Absent
E. Glucose: ↑, Insulin: ↑/Normal, C-Peptide: ↑/Normal, Ketoacidosis: Absent

Explanation: ***Glucose: ↓, Insulin: ↑, C-Peptide: ↑, Ketoacidosis: Absent*** - The patient's **hypoglycemia (15 mg/dL)**, coupled with a pancreatic tumor and recurrent episodes, strongly suggests an **insulinoma**. - An **insulinoma** is an insulin-secreting tumor, leading to **high insulin** and **C-peptide** levels in the presence of low glucose, and typically no ketoacidosis because insulin inhibits ketogenesis. *Glucose: ↑, Insulin: ↓, C-Peptide: ↓, Ketoacidosis: Present* - This profile describes **Type 1 Diabetes Mellitus** or severe insulin deficiency, where high glucose is due to lack of insulin production and subsequent diabetic ketoacidosis. - The patient's symptoms (hypoglycemia) and the presence of a pancreatic tumor producing insulin are contradictory to this profile. *Glucose: Normal, Insulin: Normal, C-Peptide: Normal, Ketoacidosis: Absent* - This profile represents a **healthy individual** with normal metabolic function, which is inconsistent with the patient's severe hypoglycemia and recurrent collapses. - It would not explain the patient's symptoms or the pancreatic tumor's function. *Glucose: ↓, Insulin: ↑, C-Peptide: ↓, Ketoacidosis: Absent* - This finding would be typical of **exogenous insulin administration** (e.g., insulin overdose) where insulin levels are high, but C-peptide (which is co-secreted with endogenous insulin) is low. - While hypoglycemia is present, the low C-peptide contradicts the presence of an endogenous insulin-secreting pancreatic tumor. *Glucose: ↑, Insulin: ↑/Normal, C-Peptide: ↑/Normal, Ketoacidosis: Absent* - These findings could be seen in conditions like **Type 2 Diabetes** with **insulin resistance** or Cushing's syndrome where glucose and insulin might be elevated, but the patient's primary presentation is severe hypoglycemia. - This profile does not align with the patient's profound hypoglycemia and clinical picture of an insulinoma.

Question 7: A patient presents to the emergency room in an obtunded state. The patient is a known nurse within the hospital system and has no history of any medical problems. A finger stick blood glucose is drawn showing a blood glucose of 25 mg/dL. The patient's daughter immediately arrives at the hospital stating that her mother has been depressed recently and that she found empty syringes in the bathroom at the mother's home. Which of the following is the test that will likely reveal the diagnosis?

A. Fasting blood glucose
B. Urine metanephrines
C. Genetic testing
D. 24 hr cortisol
E. C-peptide level (Correct Answer)

Explanation: ***C-peptide level*** - A **low C-peptide level** in the presence of **hypoglycemia** and high insulin levels confirms the diagnosis of **exogenous insulin administration** (factitious hypoglycemia). - **C-peptide** is cleaved from **proinsulin** in equimolar amounts with endogenous insulin, making it an excellent marker to differentiate endogenous insulin production from exogenous insulin injection. - In this case: **Low C-peptide + High insulin + Hypoglycemia** = exogenous insulin administration. *Fasting blood glucose* - The patient already has documented **hypoglycemia (25 mg/dL)**, so an additional fasting blood glucose test would not provide further diagnostic information about the **cause** of hypoglycemia. - A single fasting blood glucose level indicates current glucose status but **does not differentiate** between endogenous insulin overproduction (insulinoma) and exogenous insulin administration. *Urine metanephrines* - **Urine metanephrines** are used to diagnose **pheochromocytoma**, a catecholamine-secreting tumor of the adrenal medulla. - Pheochromocytoma presents with **hypertension**, palpitations, headaches, and diaphoresis—**not hypoglycemia**. - This test is not relevant to the differential diagnosis of hypoglycemia. *Genetic testing* - **Genetic testing** might be considered for rare hereditary causes of hypoglycemia, such as congenital hyperinsulinism or genetic insulinoma syndromes (e.g., MEN1). - Given the clinical context (depressed nurse with access to insulin and empty syringes found at home), **exogenous insulin administration** is far more likely than a genetic condition. - Genetic testing is not the appropriate initial diagnostic step in this scenario. *24 hr cortisol* - A **24-hour urinary cortisol** test is used to diagnose **Cushing's syndrome** (cortisol excess), not hypoglycemia. - While **adrenal insufficiency** (cortisol deficiency) can cause hypoglycemia, it typically presents with **hypotension**, **hyponatremia**, **hyperkalemia**, and **hyperpigmentation**—features not described in this case. - The clinical presentation strongly suggests insulin-related hypoglycemia rather than adrenal insufficiency.

Question 8: A 6-day-old female newborn is brought to the physician because of yellowish discoloration of her eyes and body, vomiting, and poor feeding for 3 days. She has had diarrhea for the past 2 days. She was born at 38 weeks' gestation and the antenatal period was uncomplicated. She appears lethargic. Vital signs are within normal limits. Examination shows jaundice of the skin and conjunctivae. Bilateral cataracts are present. The abdomen is soft and nontender. The liver is palpated 4-cm below the right costal margin; there is no splenomegaly. Muscle tone is decreased in all extremities. Serum glucose concentration is 37 mg/dL. Which of the following is the most appropriate recommendation to prevent long-term complications of this illness?

A. Phototherapy
B. Thiamine therapy
C. Levothyroxine therapy
D. Frequent glucose feeds
E. Stop milk feeds (Correct Answer)

Explanation: ***Stop milk feeds*** - The constellation of **jaundice**, **vomiting**, **diarrhea**, **lethargy**, **hepatomegaly**, **hypoglycemia**, **decreased muscle tone**, and **bilateral cataracts** in a newborn is highly suggestive of **galactosemia**. - **Stopping milk feeds** (specifically those containing lactose and galactose) is the primary and most crucial intervention to prevent long-term complications such as intellectual disability, liver damage, and kidney failure. *Phototherapy* - While phototherapy is used to treat **neonatal jaundice**, it addresses only the symptom of hyperbilirubinemia, not the underlying cause in galactosemia. - It would not prevent the systemic devastating effects on other organs caused by galactose and its metabolites. *Thiamine therapy* - **Thiamine therapy** is indicated for conditions like **Wernicke-Korsakoff syndrome** or **thiamine-dependent metabolic disorders**, which do not align with the presented symptoms. - There is no evidence to support its use in galactosemia. *Levothyroxine therapy* - **Levothyroxine therapy** is used for **hypothyroidism**, a condition characterized by feeding problems, jaundice, and lethargy but typically lacks the specific findings of cataracts, vomiting/diarrhea in this acute presentation, and hepatomegaly, as seen in this clinical picture. - The combination of symptoms described points more specifically to a metabolic disorder affecting galactose metabolism. *Frequent glucose feeds* - While the newborn has **hypoglycemia**, simply providing frequent glucose feeds addresses **only a symptom** and does not resolve the underlying metabolic defect in galactosemia. - Continuing milk feeds would worsen the primary disease, despite potentially correcting blood glucose temporarily.

Question 9: A newborn infant presents with severe weakness. He was born to a G1P1 mother at 40 weeks gestation with the pregnancy attended by a midwife. The mother's past medical history is unremarkable. She took a prenatal vitamin and folic acid throughout the pregnancy. Since birth, the child has had trouble breastfeeding despite proper counseling. He also has had poor muscle tone and a weak cry. His temperature is 99.5°F (37.5°C), blood pressure is 57/38 mmHg, pulse is 150/min, respirations are 37/min, and oxygen saturation is 96% on room air. Physical exam reveals poor muscle tone. The patient's sucking reflex is weak, and an enlarged tongue is noted. An ultrasound is performed, and is notable for hypertrophy of the myocardium. Which of the following is the most likely diagnosis?

A. Acid maltase deficiency (Correct Answer)
B. Familial hypertrophic cardiomyopathy
C. Clostridium tetani infection
D. Spinal muscular atrophy type I disease
E. Clostridium botulinum infection

Explanation: ***Acid maltase deficiency*** - This condition is also known as **Pompe disease**. It is a **lysosomal storage disease** that presents in infancy with **cardiomegaly**, **macroglossia**, **hypotonia**, and **respiratory failure**, all of which are consistent with the patient's presentation. - The deficiency in **acid alpha-glucosidase (acid maltase)** leads to glycogen accumulation in lysosomes, particularly in muscle cells, causing impaired muscle function, including the heart. *Familial hypertrophic cardiomyopathy* - While it causes **myocardial hypertrophy**, it typically does **not present with profound generalized hypotonia, macroglossia, or feeding difficulties** as the primary symptoms in infancy. - This condition is usually due to **sarcomeric protein mutations** and lacks the widespread systemic muscle involvement seen in Pompe disease. *Clostridium tetani infection* - This infection causes **tetanus**, characterized by **severe muscle spasms, trismus (lockjaw), and opisthotonus**, rather than hypotonia and weakness. - It would also typically involve a history of a **puncture wound or contaminated injury**, which is not mentioned. *Spinal muscular atrophy type I disease* - This is characterized by **severe hypotonia** and **muscle weakness** due to the degeneration of anterior horn cells. - However, **cardiomegaly and macroglossia are not typical features** of spinal muscular atrophy. *Clostridium botulinum infection* - This infection causes **flaccid paralysis** and weakness, usually presenting with **constipation**, **weak cry**, and **difficulty feeding**, by preventing acetylcholine release at neuromuscular junctions. - However, **cardiomyopathy and macroglossia are not characteristic** of botulism.

Question 10: A 1-year-old male with a history of recurrent pseudomonal respiratory infections and steatorrhea presents to the pediatrician for a sweat test. The results demonstrate a chloride concentration of 70 mEq/L (nl < 40 mEq/L). Which of the following defects has a similar AUTOSOMAL RECESSIVE mode of inheritance as the disorder experienced by this patient?

A. Abnormal production of type IV collagen
B. Trinucleotide repeat expansion of CAG on chromosome 4
C. Mutated gene for mitochondrial-tRNA-Lys
D. Accumulation of glycogen in the lysosome (Correct Answer)
E. Inability to convert carbamoyl phosphate and ornithine into citrulline

Explanation: ***Accumulation of glycogen in the lysosome*** - The patient's symptoms (recurrent **pseudomonal respiratory infections**, **steatorrhea**, and elevated sweat chloride) are classic for **cystic fibrosis (CF)**, an **autosomal recessive** disorder. - Accumulation of glycogen in the lysosome describes **Pompe disease (Type II Glycogen Storage Disease)**, which is also an **autosomal recessive** disorder, making this the correct answer. *Abnormal production of type IV collagen* - This defect is characteristic of **Alport syndrome**, which is predominantly **X-linked dominant** (~80-85% of cases), though autosomal recessive forms exist. - The question context and typical board exam framing classify this as X-linked, not autosomal recessive. - Alport syndrome primarily affects the kidneys, ears, and eyes, and does not present with recurrent pseudomonal infections or steatorrhea. *Trinucleotide repeat expansion of CAG on chromosome 4* - This genetic defect is responsible for **Huntington's disease**, which is an **autosomal dominant** neurodegenerative disorder. - Huntington's disease presents with chorea, cognitive decline, and psychiatric symptoms, which are distinct from CF. *Mutated gene for mitochondrial-tRNA-Lys* - A mutated gene for mitochondrial-tRNA-Lys is associated with **MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes)**, which is inherited through **maternal (mitochondrial)** inheritance. - This mode of inheritance is distinct from the autosomal recessive pattern seen in cystic fibrosis. *Inability to convert carbamoyl phosphate and ornithine into citrulline* - This describes a defect in **ornithine transcarbamylase (OTC) deficiency**, an **X-linked recessive** disorder, not autosomal recessive. - OTC deficiency leads to hyperammonemia and metabolic disturbances, without the pulmonary and gastrointestinal symptoms typical of cystic fibrosis.

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