Glycogen storage diseases

Glycogen storage diseases US Medical PG 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

Glycogen storage diseases 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.

Glycogen storage diseases US Medical PG Question 2: A 10-year-old boy is brought to the emergency department due to vomiting and weakness. He is attending a summer camp and was on a hike with the other kids and a camp counselor. His friends say that the boy skipped breakfast, and the counselor says he forgot to pack snacks for the kids during the hike. The child’s parents are contacted and report that the child has been completely healthy since birth. They also say there is an uncle who would have to eat regularly or he would have similar symptoms. At the hospital, his heart rate is 90/min, respiratory rate is 17/min, blood pressure is 110/65 mm Hg, and temperature is 37.0°C (98.6°F). Physical examination reveals a visibly lethargic child with slight disorientation to time and place. Mild hepatosplenomegaly is observed but no signs of dehydration are noted. A blood sample is drawn, and fluids are started via an intravenous line. Lab report Serum glucose 44 mg/dL Serum ketones absent Serum creatinine 1.0 mg/dL Blood urea nitrogen 32 mg/dL Alanine aminotransferase (ALT) 425 U/L Aspartate aminotransferase (AST) 372 U/L Hemoglobin (Hb%) 12.5 g/dL Mean corpuscular volume (MCV) 80 fl Reticulocyte count 1% Erythrocyte count 5.1 million/mm3 Which of the following is most likely deficient in this patient?

• A. Acyl-CoA dehydrogenase (Correct Answer)
• B. α-glucosidase
• C. Glucose-6-phosphatase
• D. Acetyl-CoA carboxylase
• E. Nicotinic acid

Glycogen storage diseases Explanation: ***Acyl-CoA dehydrogenase*** - This patient presents with **hypoglycemia** (44 mg/dL) and **absent ketone bodies** after prolonged fasting, along with elevated **liver transaminases** and **hepatosplenomegaly**, which are classic signs of a **fatty acid oxidation disorder**. - A deficiency in **acyl-CoA dehydrogenase**, particularly **medium-chain acyl-CoA dehydrogenase (MCAD)**, prevents adequate fatty acid breakdown for energy and ketone production, leading to **hypoketotic hypoglycemia** during periods of fasting. *α-glucosidase* - A deficiency in **α-glucosidase** (Pompe disease) leads to the accumulation of **glycogen** in lysosomes, primarily affecting muscles, heart, and liver. - While it can cause hepatomegaly and muscle weakness, it typically presents with **cardiomyopathy** and does not directly cause hypoketotic hypoglycemia. *Glucose-6-phosphatase* - A deficiency in **glucose-6-phosphatase** (Von Gierke disease) is a type of **glycogen storage disease** characterized by severe **fasting hypoglycemia with lactic acidosis**, **massive hepatomegaly**, and **hyperlipidemia**. - Unlike fatty acid oxidation disorders, Von Gierke disease typically presents with **lactic acidosis** as the predominant metabolic derangement, and patients often have a **doll-like face** and **growth retardation** from chronic presentation. *Acetyl-CoA carboxylase* - **Acetyl-CoA carboxylase** is a key enzyme in **fatty acid synthesis**, not fatty acid oxidation. - A deficiency would primarily impair the body's ability to synthesize fatty acids, which is not consistent with the hypoketotic hypoglycemia observed here. *Nicotinic acid* - **Nicotinic acid** (niacin or vitamin B3) is a precursor to **NAD+** and **NADP+**, coenzymes involved in various metabolic reactions, including fatty acid synthesis and breakdown. - While a deficiency (pellagra) can cause dermatitis, diarrhea, and dementia, it does not directly lead to **hypoketotic hypoglycemia** or fatty liver disease.

Glycogen storage diseases US Medical PG Question 3: A 27-year-old Hispanic G2P1 presents for a routine antepartum visit at 26 weeks gestation. She has no complaints. The vital signs are normal, the physical examination is within normal limits, and the gynecologic examination corresponds to 25 weeks gestation. The oral glucose tolerance test (OGTT) with a 75-g glucose load is significant for a glucose level of 177 mg/dL at 1 hour and 167 mg/dL at 2 hour. The fasting blood glucose level is 138 mg/dL (7.7 mmol/L), and the HbA1c is 7%. Which of the following represents the proper initial management?

• A. Sitagliptin
• B. Dietary and lifestyle modification
• C. Metformin
• D. Glyburide
• E. Insulin (Correct Answer)

Glycogen storage diseases Explanation: **Insulin** - The patient's **fasting glucose of 138 mg/dL** and **HbA1c of 7%** indicate pre-existing **Type 2 Diabetes Mellitus**, not just gestational diabetes. Both values exceed the diagnostic thresholds for overt diabetes in pregnancy. - **Insulin** is the preferred initial pharmacologic treatment for **overt diabetes in pregnancy** because it does not cross the placenta, ensuring fetal safety, and is highly effective in controlling maternal glucose levels. *Sitagliptin* - **Sitagliptin** is a **DPP-4 inhibitor** and is not recommended during pregnancy due to limited safety data and the availability of safer alternatives. - Oral hypoglycemic agents are generally avoided as first-line therapy for established diabetes in pregnancy due to potential for placental transfer and adverse fetal effects. *Dietary and lifestyle modification* - While crucial, **dietary and lifestyle modification** alone are insufficient for managing overt diabetes with such high fasting glucose and HbA1c levels. - These measures are usually the first step for **gestational diabetes**, but a patient with overt diabetes requires immediate pharmacologic intervention to prevent complications. *Metformin* - **Metformin** can be used in pregnancy but is primarily considered for **gestational diabetes** or as an alternative to insulin if the patient has milder hyperglycemia, or if insulin is poorly tolerated. - Given the patient's significantly elevated fasting glucose and HbA1c, **insulin** is a more effective and immediate treatment to achieve glycemic control and reduce risks. *Glyburide* - **Glyburide** is an **oral sulfonylurea** that can cross the placenta, leading to potential fetal hyperinsulinemia and neonatal hypoglycemia. - Its use in pregnancy is generally discouraged due to these risks, making **insulin** a safer and more appropriate choice.

Glycogen storage diseases US Medical PG Question 4: A 12-year-old girl comes to the clinic with a grossly enlarged abdomen. She has a history of frequent episodes of weakness, sweating, and pallor that are eliminated by eating. Her development has been slow. She started to walk unassisted at 2 years and was not performing well at school. Physical examination reveals a blood pressure of 100/60 mm Hg, heart rate of 80/min, and temperature of 36.9°C (98.4℉). On physical examination, the liver is enlarged, firm, and palpable up to the pelvis. The spleen and kidney are not palpable. Laboratory investigation reveals low blood glucose and pH with high lactate, triglycerides, ketones, and free fatty acids. The liver biopsy revealed high glycogen content. Hepatic glycogen structure was normal. The enzyme assay performed on the biopsy tissue revealed very low glucose-6-phosphatase levels. What is the most likely diagnosis?

• A. Pompe's disease
• B. Cori's disease
• C. Hereditary hemochromatosis
• D. Von-Gierke's disease (Correct Answer)
• E. McArdle disease

Glycogen storage diseases Explanation: ***Von-Gierke's disease*** - The combination of **hepatomegaly**, **hypoglycemia** (causing weakness, sweating, pallor), **lactic acidosis**, **hyperlipidemia**, and elevated ketones points to a severe defect in glucose metabolism. - **Very low glucose-6-phosphatase levels** on liver biopsy and normal hepatic glycogen structure are pathognomonic for Von-Gierke's disease (Glycogen Storage Disease Type I). *Pompe's disease* - This is a **lysosomal storage disease** affecting **alpha-1,4-glucosidase**, leading to glycogen accumulation in lysosomes. - It primarily affects the **heart** and skeletal muscles and would not present with severe lactic acidosis and hyperlipidemia. *Cori's disease* - This is **Glycogen Storage Disease Type III**, caused by a deficiency in the **debranching enzyme** (amylo-alpha-1,6-glucosidase). - While it can cause hepatomegaly and hypoglycemia, the hepatic glycogen structure would be abnormal due to incompletely debranched glycogen, and glucose-6-phosphatase levels would be normal. *Hereditary hemochromatosis* - This is an **iron overload disorder** leading to iron deposition in organs like the liver, heart, and pancreas. - It would present with symptoms related to organ damage from iron accumulation, such as liver cirrhosis and diabetes, not the metabolic derangements seen here. *McArdle disease* - This is **Glycogen Storage Disease Type V**, due to a deficiency in **muscle glycogen phosphorylase**. - It primarily causes exercise-induced muscle pain, cramping, and fatigue due to an inability to break down muscle glycogen for energy, not systemic metabolic disturbances or hepatomegaly.

Glycogen storage diseases US Medical PG Question 5: A 49-year-old woman presents to the family medicine clinic with concerns about her weight. She has been constantly gaining weight for a decade now as she has not been able to control her diet. She has tried exercising but says that she is too lazy for this method of weight loss to work. Her temperature is 37° C (98.6° F), respirations are 15/min, pulse is 67/min, and blood pressure is 122/88 mm Hg. Her BMI is 30. Her labs from her past visit show: Fasting blood glucose: 149 mg/dL Glycated hemoglobin (HbA1c): 9.1% Triglycerides: 175 mg/dL LDL-Cholesterol: 102 mg/dL HDL-Cholesterol: 35 mg/dL Total Cholesterol: 180 mg/dL Serum creatinine: 1.0 mg/dL BUN: 12 mg/dL Serum: Albumin: 4.2 gm/dL Alkaline phosphatase: 150 U/L Alanine aminotransferase: 76 U/L Aspartate aminotransferase: 88 U/L After discussing the long term issues that will arise if her health does not improve, she agrees to modify her lifestyle and diet. Which of the following would be the best pharmacotherapy for this patient?

• A. Insulin
• B. Metformin (Correct Answer)
• C. Dietary modification alone
• D. Sitagliptin
• E. Glipizide

Glycogen storage diseases Explanation: ***Metformin*** - This patient has newly diagnosed **type 2 diabetes mellitus** (Fasting blood glucose 149 mg/dL, HbA1c 9.1%) in the setting of obesity (BMI 30). **Metformin** is the **first-line pharmacotherapy** for type 2 diabetes due to its efficacy, favorable safety profile, and potential for weight neutrality or modest weight loss. - Metformin works by **decreasing hepatic glucose production**, decreasing intestinal glucose absorption, and increasing insulin sensitivity. *Insulin* - While insulin is highly effective in lowering blood glucose, it is typically reserved for patients with **very high HbA1c** (often >10%), **symptomatic hyperglycemia**, or those who have failed oral pharmacotherapy, it can also cause **weight gain**. - Initiating insulin as first-line therapy can be overly aggressive and may lead to **hypoglycemia** in patients who can respond to oral agents. *Dietary modification alone* - Although **lifestyle changes** (diet and exercise) are crucial and can be remarkably effective, this patient's **HbA1c of 9.1%** indicates that **monotherapy with diet and exercise alone is insufficient** to achieve glycemic control. - Pharmacotherapy is generally recommended for HbA1c levels **above 7.5%**, even with a commitment to lifestyle changes. *Sitagliptin* - **Sitagliptin** is a **DPP-4 inhibitor** that increases insulin secretion and decreases glucagon secretion in a glucose-dependent manner. - It is often considered a **second-line agent** or an add-on therapy, as its HbA1c-lowering effect is generally less potent than metformin. *Glipizide* - **Glipizide** is a **sulfonylurea** that works by stimulating insulin release from pancreatic beta cells. - It can cause **weight gain** and has a significant risk of **hypoglycemia**, making it a less favorable first-line agent, especially in an obese patient, compared to metformin.

Glycogen storage diseases US Medical PG Question 6: A 15-year-old boy comes to the physician because of severe muscle cramps and pain for 3 months. He first noticed these symptoms while attending tryouts for the high school football team. Since then, he becomes easily fatigued and has severe muscle pain and swelling after 10 minutes of playing. However, after a brief period of rest, the symptoms improve, and he is able to return to the game. Two days ago, he had an episode of reddish-brown urine after playing football. There is no family history of serious illness. He appears healthy. Vital signs are within normal limits. Physical and neurological examinations show no abnormalities. Serum creatine kinase concentration is 333 U/L. Urinalysis shows: Blood 2+ Protein negative Glucose negative RBC negative WBC 1–2/hpf Which of the following is the most likely cause of this patient's symptoms?

• A. CTG repeat in the DMPK gene
• B. Myophosphorylase deficiency (Correct Answer)
• C. Dystrophin gene mutation
• D. Thyroid hormone deficiency
• E. Acid maltase deficiency

Glycogen storage diseases Explanation: ***Myophosphorylase deficiency*** - This condition (also known as **McArdle disease**) presents with **exercise-induced muscle cramps, pain, and fatigue** immediately after initiating activity, with a "second wind" phenomenon where symptoms improve after resting. - The elevated **creatine kinase** and **reddish-brown urine** (indicating **myoglobinuria** due to rhabdomyolysis) are classic findings after strenuous activity in this glycogen storage disorder. *CTG repeat in the DMPK gene* - This describes **myotonic dystrophy type 1**, which presents with **myotonia** (delayed muscle relaxation), muscle weakness, and often involves multiple organ systems. - While it causes muscle weakness, it does not typically present with acute, exercise-induced pain, cramping, and rhabdomyolysis in this manner. *Dystrophin gene mutation* - This is characteristic of **Duchenne or Becker muscular dystrophy**, which are progressive muscle weakness disorders. - They typically cause **progressive proximal muscle weakness** and atrophy, not acute, intermittent, exercise-induced pain and cramping with a "second wind" phenomenon. *Thyroid hormone deficiency* - **Hypothyroidism** can cause muscle cramps, weakness, and elevated creatine kinase, but these symptoms are usually chronic and progressive, not acutely exercise-induced with improvement after a short rest. - It would also present with other systemic symptoms like fatigue, weight gain, and cold intolerance, which are not described. *Acid maltase deficiency* - Also known as **Pompe disease**, this is a glycogen storage disorder that primarily affects infants and can present in adults with **proximal muscle weakness**, respiratory insufficiency, and cardiac involvement. - It does not typically present with acute, exercise-induced muscle cramps, pain, and rhabdomyolysis followed by a "second wind" phenomenon like McArdle disease.

Glycogen storage diseases US Medical PG Question 7: 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

Glycogen storage diseases 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.

Glycogen storage diseases US Medical PG Question 8: A 16-year-old boy comes to the physician because of muscle weakness and cramps for 5 months. He becomes easily fatigued and has severe muscle pain and swelling after 15 minutes of playing basketball with his friends. The symptoms improve after a brief period of rest. After playing, he sometimes also has episodes of reddish-brown urine. There is no family history of serious illness. Serum creatine kinase concentration is 950 U/L. Urinalysis shows: Blood 2+ Protein negative Glucose negative RBC negative WBC 1–2/hpf Which of the following is the most likely underlying cause of this patient's symptoms?

• A. Medium-chain acyl-CoA dehydrogenase deficiency
• B. Myophosphorylase deficiency (Correct Answer)
• C. Low levels of triiodothyronine and thyroxine
• D. Acid maltase deficiency
• E. CTG repeat in the DMPK gene

Glycogen storage diseases Explanation: ***Myophosphorylase deficiency*** - This condition (McArdle disease) is an **autosomal recessive disorder** of glycogen metabolism characterized by a defect in **glycogenolysis**, specifically the breakdown of muscle glycogen. This leads to impaired energy production during exercise. - The classic presentation includes **exercise-induced muscle pain, stiffness, cramps, fatigue**, and sometimes **myoglobinuria** (reddish-brown urine due to myoglobin release from damaged muscle), which is consistent with the patient's symptoms and elevated **creatine kinase**. *Medium-chain acyl-CoA dehydrogenase deficiency* - This is a disorder of **fatty acid oxidation** that primarily affects the liver, leading to episodes of **hypoketotic hypoglycemia** during fasting or illness. - It does not typically present with isolated exercise-induced muscle pain and myoglobinuria. *Low levels of triiodothyronine and thyroxine* - **Hypothyroidism** can cause generalized muscle weakness, fatigue, and muscle cramps, but it is usually associated with other systemic symptoms like weight gain, cold intolerance, and constipation. - While it can cause elevated CK, it generally does not present with acute, exercise-induced muscle pain and myoglobinuria in the manner described. *Acid maltase deficiency* - This (Pompe disease) is a lysosomal storage disorder affecting glycogen metabolism, but it results from a deficiency of **acid alpha-glucosidase (acid maltase)**. - The infantile form presents with severe hypotonia and cardiomyopathy, while the juvenile and adult forms typically cause **proximal muscle weakness** and respiratory insufficiency, rather than exercise-induced muscle pain and myoglobinuria. *CTG repeat in the DMPK gene* - This genetic defect is associated with **myotonic dystrophy type 1 (Steinert disease)**, an autosomal dominant disorder. - Key features include **myotonia** (delayed relaxation of muscles), muscle weakness, cataracts, and cardiac conduction abnormalities, which are distinct from the patient's presentation of exercise-induced cramps and myoglobinuria without myotonia.

Glycogen storage diseases US Medical PG Question 9: 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)

Glycogen storage diseases 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.

Glycogen storage diseases US Medical PG Question 10: 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

Glycogen storage diseases 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.

Glycogen storage diseases Flashcard 1 of 10

Question: Which glycogen storage disorder is associated with severe fasting hypoglycemia? _____

Answer: Von Gierke disease

Glycogen storage diseases Flashcard 2 of 10

Question: The hallmark of what glycogen storage disease is a flat venous lactate curve with a rise in ammonia levels during exercise?_____

Answer: McArdle disease

Glycogen storage diseases Flashcard 3 of 10

Question: Which glycogen storage disease has an increased risk for gout? _____

Answer: Von Gierke disease

Glycogen storage diseases Flashcard 4 of 10

Question: Glucocorticoids increase hepatic _____ storage

Answer: glycogen

Glycogen storage diseases Flashcard 5 of 10

Question: Which glycogen storage disorder is associated with accumulation of limit dextrin-like structures? _____

Answer: Cori disease

Glycogen storage diseases Flashcard 6 of 10

Question: Von Gierke disease is characterized by severe fasting _____

Answer: hypoglycemia

Glycogen storage diseases Flashcard 7 of 10

Question: glycogen synthesis

Answer: glycogen synthase

Glycogen storage diseases Flashcard 8 of 10

Question: glycogenolysis

Answer: glycogen phosphorylase

Glycogen storage diseases Flashcard 9 of 10

Question: McArdle's disease (GSD type V)

Answer:

Extra Information: painful muscle cramps, myoglobinuria with strenuous exerciseglycogen accumulation in muscleARskeletal muscle glycogen phosphorylasemnemonic: Very Bad Carbohydrate Metabolism (the glycogen storage diseases in order)

Glycogen storage diseases Flashcard 10 of 10

Question: Cori's disease (GSD type III)

Answer:

Extra Information: hepatomegalyfasting hypoglycemia, increased hepatic glycogen stores, normal blood lactate levelsARglycogen debranching enzymemnemonic: Very Bad Carbohydrate Metabolism (the glycogen storage diseases in order)