What causes hypoglycemic seizures in children?

Causes of Hypoglycemic Seizures in Children

Hypoglycemic seizures in children result from inadequate glucose delivery to the brain, with the most common causes being insulin excess (in diabetic children), prolonged fasting with intercurrent illness (particularly gastroenteritis), ketotic hypoglycemia, and less commonly, metabolic disorders such as glycogen storage diseases or fatty acid oxidation defects. 1, 2, 3

Primary Etiologic Categories

Insulin-Related Causes (Diabetic Children)

• Insulin overdose is the leading cause of severe hypoglycemia with seizures in children with established diabetes, accounting for the majority of hypoglycemic emergencies requiring emergency intervention 1, 4, 5
• Insulin excess relative to food intake or energy expenditure can cause severe hypoglycemia with coma, seizures, or neurologic impairment 4
• In children with insulin-dependent diabetes, 31% experience severe hypoglycemia (defined by coma or convulsion), with 39% of these episodes occurring during sleep 5
• Intentional insulin omission followed by overcorrection is a common pattern in adolescents with recurrent episodes 1

Fasting-Related Causes (Non-Diabetic Children)

• Gastroenteritis or other infectious diseases causing protracted fasting accounts for 86.32% of hypoglycemic presentations in pediatric emergency departments 3
• These children typically have adequate metabolic systems but insufficient glucose intake during illness 3
• Ketotic hypoglycemia is the most common cause of hypoglycemia outside the neonatal period in non-diabetic children, typically occurring after prolonged fasting in younger children with limited glycogen stores 6, 3

Metabolic and Endocrine Disorders

• Glycogen storage diseases (GSD) present with hypoglycemia, elevated liver enzymes, and hepatomegaly, though ultrasound may initially appear normal as these cause functional rather than structural abnormalities 2
• Critical diagnostic features include ketone status, lactate levels, uric acid, and response to glucagon administration (0.03 mg/kg, max 1 mg) 2
• Fatty acid oxidation defects should be suspected when hypoglycemia occurs with hypoketotic features 2, 7
• Hypopituitarism with deficiencies in cortisol or growth hormone can cause persistent hypoglycemia, particularly in neonates 6
• Hyperinsulinism (congenital or acquired) causes severe, recurrent hypoglycemia without appropriate ketone production 6, 8

Medication and Toxin-Related

• Antidiabetic medications (accidental ingestion or intentional overdose) 1
• Other medications affecting glucose metabolism 1, 4

Critical Diagnostic Approach

Immediate Assessment During Hypoglycemic Episode

Before treating hypoglycemia (if the child is stable enough), draw critical diagnostic samples including blood for glucose, insulin, cortisol, growth hormone, lactate, free fatty acids, beta-hydroxybutyrate, acetoacetate, liver function tests, ammonia, and urine for ketones and organic acids. 2 However, never delay glucose administration if the child is symptomatic or glucose <50 mg/dL, as brain injury prevention takes absolute priority. 2

Key Diagnostic Features to Differentiate Causes

• Presence or absence of ketones: Hyperinsulinism and fatty acid oxidation defects present with hypoketotic hypoglycemia, while ketotic hypoglycemia and most fasting states show appropriate ketone elevation 2, 6
• Timing of onset: Clinical onset within 12 hours is significantly associated with metabolic disorders (adjusted OR 3.98) 3
• Level of consciousness: Impaired consciousness on AVPU scale is significantly associated with metabolic causes (adjusted OR 2.50) 3
• Associated findings: Elevated liver enzymes suggest glycogen storage disease or fatty acid oxidation defects; hepatomegaly supports GSD 2

High-Risk Scenarios Requiring Heightened Suspicion

Severe Malaria

• Hypoglycemia (blood glucose <3 mmol/L) may precipitate seizures or posturing in children with severe malaria 1
• Should be considered in any child with seizures in endemic areas 1

Recurrent Episodes

• Children with recurrent severe hypoglycemic seizures require psychiatric evaluation, as this pattern is associated with higher incidence of depression, eating disorders, and intentional insulin omission 1
• Hypoglycemia unawareness develops after repeated episodes due to defective counterregulation, with failure of adrenergic responses, placing children at greater risk for seizures without warning symptoms 1, 9

Age-Specific Vulnerabilities

• Children younger than 5-7 years have immature counterregulatory mechanisms and may lack cognitive capacity to recognize hypoglycemic symptoms, placing them at higher risk for seizures 1
• Young children are at risk for permanent cognitive impairment after episodes of severe hypoglycemia with seizures 1

Common Pitfalls to Avoid

• Do not assume normal liver ultrasound excludes metabolic liver disease, as glycogen storage diseases cause functional abnormalities initially, with fibrosis and adenomas developing over years 2
• Do not rely on bedtime glucose levels to predict nocturnal hypoglycemia, as they are poor predictors of overnight episodes that commonly cause seizures during sleep 1, 5
• Do not overlook the possibility of metabolic disorders in children presenting with severe hypoglycemia (glucose <45 mg/dL), impaired consciousness, and recent symptom onset, even if infection is present 3
• Recognize that early warning symptoms may be absent in children with long diabetes duration, intensified control, or those on beta-blockers, resulting in seizures as the first manifestation 4