What is the diagnosis and recommended management for a 12-year-old female presenting with morning dizziness, tachycardia, chest pain, and blurred vision that resolve after eating, along with hives, nocturnal muscle spasms, elevated liver enzymes, vitamin D deficiency, and abnormal fasting insulin and glucose levels?

Diagnosis and Management

Primary Diagnosis

This 12-year-old female most likely has fasting hypoglycemia, potentially secondary to a glycogen storage disease (GSD), given the constellation of morning symptoms that resolve with eating, markedly elevated liver enzymes (AST 180, ALT 257), muscle spasms, and abnormal metabolic parameters. 1

The clinical presentation strongly suggests hypoglycemia as the unifying diagnosis:

• Morning dizziness, tachycardia, chest pain, and blurred vision that resolve after eating are classic autonomic and neuroglycopenic symptoms of hypoglycemia, with the timing of symptom relief (within 15-30 minutes of eating) being diagnostic for hypoglycemia as the underlying cause 1
• Nocturnal muscle spasms (calf cramps) occur in glycogen storage diseases due to impaired muscle energy metabolism during fasting states when hypoglycemia develops 1
• Markedly elevated transaminases (AST 180, ALT 257) combined with hypoglycemia and muscle symptoms should prompt immediate workup for glycogen storage disease 2, 1

Critical Diagnostic Workup

Immediate laboratory evaluation is essential and should include:

• Fasting blood glucose, lactate, uric acid, and complete hepatic profile to differentiate between GSD subtypes 1
• Beta-hydroxybutyrate and ketone levels during a hypoglycemic episode—hyperketonemia with fasting suggests GSD III, whereas elevated lactate suggests GSD I 1
• Muscle enzymes (CK, aldolase) to assess for myopathy associated with GSD IIIa 2, 1
• Plasma carnitine, acylcarnitine profile, and urine organic acids to rule out other metabolic disorders 1
• Abdominal ultrasound to assess for hepatomegaly, which is typically present in GSD and helps distinguish from other causes 1

Secondary Considerations

The elevated fasting insulin (26.9) with normal glucose (81) warrants additional investigation:

• This pattern could represent insulin resistance, though the clinical picture is dominated by hypoglycemic symptoms rather than hyperglycemia 3, 4
• Rule out insulin autoimmune syndrome (IAS) with anti-insulin antibody testing, though this is rare in Caucasian populations and typically presents with postprandial rather than fasting hypoglycemia 5

The hives (urticaria) may be:

• A separate allergic process requiring independent evaluation 1
• Potentially related to stress response during hypoglycemic episodes, though this is less common 1

Vitamin D deficiency (13 ng/mL) requires treatment but is unlikely related to the liver enzyme elevation in this otherwise healthy adolescent without known liver disease 6

Immediate Management

For acute symptom relief:

• Administer 15-20 grams of rapid-acting carbohydrates (glucose tablets, juice, or regular soda) when morning symptoms occur to resolve dizziness, tachycardia, and other autonomic symptoms 1
• Never leave the patient unsupervised during hypoglycemia until treatment has been administered and symptoms have resolved 2
• For severe hypoglycemia with confusion or inability to eat, glucagon or intravenous glucose is required 1, 7

Preventive measures pending definitive diagnosis:

• Implement frequent feedings with complex carbohydrates every 2-3 hours during the day, with a substantial bedtime snack containing protein and complex carbohydrates 1
• Consider uncooked cornstarch supplementation (0.5-1 g/kg at bedtime) if GSD is confirmed, as this provides sustained glucose release for 4-6 hours 2, 1
• Avoid prolonged fasting and ensure the patient eats immediately upon waking 2
• Provide a Medic-Alert bracelet and emergency letter from the physician detailing the hypoglycemia risk 2

Monitoring Strategy

Implement home blood glucose monitoring:

• Check fasting blood glucose upon waking before any food intake 1
• Monitor during symptomatic episodes to document hypoglycemia and establish the pattern 1
• Check blood glucose if symptoms occur during the night or if morning headache, confusion, or behavior changes are present 2, 7

Critical Pitfalls to Avoid

Do not dismiss symptoms as anxiety or panic attacks despite the autonomic features (palpitations, chest discomfort)—the clear temporal relationship to fasting and resolution with eating is diagnostic for hypoglycemia 1

Do not delay evaluation with a metabolic specialist—the combination of hypoglycemia, elevated liver enzymes, and muscle symptoms requires urgent subspecialty assessment 2, 1

Avoid medications that can worsen hypoglycemia including beta-blockers (which would mask hypoglycemic symptoms), insulin secretagogues, and alcohol 2

Do not recommend aggressive exercise or contact sports until hepatomegaly is ruled out and metabolic status is stabilized, as hepatomegaly increases risk of hepatic injury 2

Definitive Diagnostic Testing

If initial workup suggests GSD:

• Genetic testing for GSD III (AGL gene) and other GSD subtypes provides definitive diagnosis 2
• Liver biopsy with enzyme analysis may be considered if genetic testing is inconclusive, though this is rarely necessary with modern molecular diagnostics 2

Cardiology evaluation is essential if GSD III is confirmed, as GSD IIIa causes hypertrophic cardiomyopathy in a significant proportion of patients 2