A 16-year-old woman presents to the emergency department for evaluation of acute vomiting and abdominal pain. Onset was roughly 3 hours ago while she was sleeping. She has no known past medical history. Her family history is positive for hypothyroidism and diabetes mellitus in her maternal grandmother. On examination, she is found to have fruity breath and poor skin turgor. She appears fatigued and her consciousness is slightly altered. Laboratory results show a blood glucose level of 691 mg/dL, sodium of 125 mg/dL, and elevated serum ketones. Of the following, which is the next best step in patient management?

Administer IV fluids and insulin

Initiate basal-bolus insulin regimen

Initiate insulin glargine 10 units at bedtime only

Initiate oral antidiabetic medications

Initiate insulin aspart at mealtimes only

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?

Medium-chain acyl-CoA dehydrogenase deficiency

Low levels of triiodothyronine and thyroxine

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?

Familial hypertrophic cardiomyopathy

Spinal muscular atrophy type I disease

Clostridium botulinum infection

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?

Increased LDL and decreased HDL

Increased pigmentation in flexural areas

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?

Accumulation of glycogen in the lysosome

Abnormal production of type IV collagen

Trinucleotide repeat expansion of CAG on chromosome 4

Mutated gene for mitochondrial-tRNA-Lys

Inability to convert carbamoyl phosphate and ornithine into citrulline

Management strategies for GSDs Revision – USMLE Biochemistry

Dietary Management - The Cornerstone Strategy

Goal: Maintain euglycemia & prevent hypoglycemia.
Uncooked Cornstarch (UCCS): Cornerstone for GSD I, III, IV, VI, IX.
- Provides slow, steady glucose release.
- Dose: 1.6-2.5 g/kg every 4-6 hours.
- Must be uncooked and mixed in cool water.
Dietary Restrictions (GSD I):
- Strict avoidance of fructose, sucrose, galactose, & lactose.
- Prevents worsening of lactic acidosis & hyperlipidemia.
Specific Modifications:
- GSD III: High-protein diet supports gluconeogenesis.
- GSD V (McArdle): Pre-exercise sucrose (~30g) can improve exercise tolerance.

⭐ Uncooked cornstarch (UCCS) therapy revolutionized GSD I management, dramatically improving survival and reducing reliance on continuous nocturnal feedings.

Pharmacotherapy & ERT - The Medical Arsenal

GSD I (von Gierke's Disease):
- Allopurinol: Manages hyperuricemia to prevent gout and nephropathy.
- Citrate supplements: Alkalinize urine, reducing risk of uric acid stones.
- Lipid-lowering agents: Statins or fibrates for severe hypertriglyceridemia.
- G-CSF (Filgrastim): For neutropenia and recurrent infections in GSD Ib.
GSD II (Pompe Disease):
- Enzyme Replacement Therapy (ERT): The cornerstone of treatment.
- Alglucosidase alfa (Myozyme®, Lumizyme®): A recombinant human acid α-glucosidase (GAA) administered via regular IV infusions.
GSD V (McArdle's Disease):
- Pre-exercise sucrose/glucose: Provides an alternative, readily available fuel source.
- Vitamin B6 (Pyridoxine): Cofactor for muscle glycogen phosphorylase; may offer some benefit.

⭐ In Pompe disease, ERT dramatically improves hypertrophic cardiomyopathy and survival in infants, but its efficacy on skeletal muscle function in late-onset disease is more variable.

Therapeutic strategies for Glycogen Storage Diseases

Monitoring & Complications - The Long-Term View

Routine Surveillance: Lifelong, multidisciplinary follow-up is key.
- Growth: Serial height/weight, bone age.
- Biochemical: Glucose, lactate, lipid panel, uric acid.
- Liver: Annual LFTs & ultrasound (from age 10 for GSD I).
- Renal: Annual urinalysis (microalbuminuria), creatinine, electrolytes.
- Cardiac: ECG/ECHO for GSD III, IV.
Long-Term Complications:
- Hepatic: Hepatic adenomas (GSD I) → risk of hemorrhage or malignant transformation to HCC.
- Renal: Nephromegaly, progressive renal insufficiency, Fanconi syndrome.
- Bone: Osteopenia/osteoporosis.
- Hematologic: Anemia, platelet dysfunction.

MRI of hepatic adenoma in Glycogen Storage Disease Type I

⭐ In GSD I, hepatic adenomas can regress with strict dietary therapy, but the risk of malignant transformation into hepatocellular carcinoma (HCC) remains a lifelong concern.

High‑Yield Points - ⚡ Biggest Takeaways

The primary goal is to maintain euglycemia and prevent hypoglycemia.

Management relies on dietary therapy, including frequent small meals and continuous nocturnal feeds.

Uncooked cornstarch is a cornerstone, providing slow-release glucose, especially overnight.

In GSD I (von Gierke), it's crucial to avoid fructose and galactose.

Allopurinol is used to treat the hyperuricemia associated with GSD I.

For GSD V (McArdle), management includes sucrose before exercise.

GSD II (Pompe) is uniquely treated with enzyme replacement therapy (ERT).

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play