What is the diagnosis and management for a pediatric patient with morning tachycardia, dizziness, hyperinsulinemia, normal fasting glucose, and elevated liver enzymes?

Hyperinsulinemic Hypoglycemia with Elevated Liver Enzymes: Likely Glycogen Storage Disease

This 12-year-old presents with a classic constellation of findings suggesting a glycogen storage disorder, most likely GSD Type I or III, requiring urgent genetic testing, metabolic workup, and dietary management to prevent life-threatening hypoglycemia and long-term complications.

Diagnostic Reasoning

The combination of hyperinsulinemia (insulin 26.9), elevated C-peptide (3.8), normal fasting glucose (81), and markedly elevated transaminases (AST 180, ALT 257) in a child with morning tachycardia and dizziness points strongly toward a glycogen storage disease rather than primary hyperinsulinism 1.

Key Distinguishing Features

Morning symptoms are critical: The tachycardia and dizziness upon waking represent counter-regulatory responses to nocturnal hypoglycemia after the overnight fast, which is pathognomonic for disorders of glucose homeostasis 1. This timing distinguishes GSD from other causes of elevated liver enzymes 1.

Elevated transaminases with normal glucose: The markedly elevated AST (180) and ALT (257) with a relatively normal fasting glucose (81) is characteristic of GSD Type III, where transaminases are often 2-3 times upper limits of normal and frequently exceed 500 IU/L 1. In GSD Type I, transaminases are typically less elevated 1.

Hyperinsulinemia pattern: The elevated insulin and C-peptide with normal glucose suggests compensatory hyperinsulinemia secondary to insulin resistance, which is commonly associated with fatty liver disease seen in glycogen storage disorders 2. This is distinct from primary hyperinsulinism, where glucose would be significantly lower 1.

Immediate Diagnostic Workup Required

Critical Laboratory Tests

• Fasting metabolic panel: Measure lactate, uric acid, cholesterol, triglycerides, and beta-hydroxybutyrate during a supervised brief fast 1
• GSD Type I findings: Hypoglycemia with lactic acidosis, hyperuricemia, hypercholesterolemia, and hypertriglyceridemia 1
• GSD Type III findings: Hypoglycemia with elevated ketones (beta-hydroxybutyrate), normal lactate and uric acid, with markedly elevated transaminases 1

Genetic Testing

Confirm diagnosis with gene sequencing: Full sequencing of G6PC (GSD Ia), SLC37A4 (GSD Ib), and AGL (GSD III) genes should be performed immediately 1. Genetic testing has replaced liver biopsy as the gold standard for diagnosis 1.

Additional Workup

• Creatine kinase (CK): Elevated CK suggests GSD Type IIIa with muscle involvement 1
• Lipid profile and complete blood count: Check for hyperlipidemia and neutropenia (suggests GSD Ib) 1
• Liver ultrasound: Assess for hepatomegaly, fatty infiltration, and adenomas 3

Urgent Management Priorities

Prevent Life-Threatening Hypoglycemia

Immediate dietary intervention is essential: Avoidance of fasting is the cornerstone of treatment to prevent hypoglycemia, lactic acidosis, and potential seizures, permanent brain damage, or death 1.

For GSD Type I (if confirmed):

• Frequent feedings: Small, frequent meals high in complex carbohydrates (60-70% of calories) distributed over 24 hours 1
• Overnight management: Continuous overnight gastric feedings or cornstarch supplementation to maintain blood glucose ≥70 mg/dL 1, 3
• Dietary restrictions: Limit or avoid fructose and galactose (sucrose, lactose, fruit, juice, dairy) as these worsen metabolic abnormalities 1
• Nasogastric tube training: Parents should be trained in NG tube insertion for emergency glucose administration during illness 1

For GSD Type III (if confirmed):

• High-protein diet: 25% of total calories from protein, <50% from complex carbohydrates, avoiding simple sugars 1
• Overnight support: Bedtime snack with protein (low-fat milk with protein powder) or continuous enteral feeding for those with myopathy 1
• Cornstarch supplementation: Introduce as early as first year of life if hypoglycemia is present 1

Metabolic Dietitian Consultation

Mandatory specialist involvement: A metabolic dietitian must be consulted immediately to design an individualized feeding plan and monitor for micronutrient deficiencies 1.

Long-Term Monitoring and Complications

Hepatic Complications

• Hepatic adenomas: Occur in 16-75% of GSD patients and require regular ultrasound surveillance every 6-12 months 3
• Hepatocellular carcinoma risk: Screen with ultrasound and alpha-fetoprotein, though AFP may remain normal in GSD III 1, 3
• Cirrhosis: Can develop in both GSD I and III, requiring monitoring for portal hypertension and liver synthetic function 1

Avoid Estrogen-Based Contraceptives

Critical in adolescent females: Estrogen increases adenoma growth risk and should be avoided 3.

Cardiac and Muscle Monitoring

For GSD Type IIIa: Regular echocardiograms and CK monitoring are needed as cardiomyopathy and progressive myopathy can develop 1.

Common Pitfalls to Avoid

• Do not perform glucagon stimulation test: This can cause acute metabolic decompensation with severe lactic acidosis in GSD Type I and is not recommended for diagnosis 1
• Do not delay genetic testing: Liver biopsy is no longer necessary and genetic testing is more definitive and less invasive 1
• Do not miss overnight hypoglycemia: The normal fasting glucose at presentation does not exclude dangerous nocturnal hypoglycemia—continuous glucose monitoring may be helpful 1
• Do not attribute symptoms to other causes: Morning tachycardia and dizziness in the context of these labs should not be dismissed as orthostatic hypotension or anxiety 1