Causes of Hypoglycemic Seizures in Children
In children with established diabetes, insulin overdose is the leading cause of hypoglycemic seizures, while in non-diabetic children, hyperinsulinism (particularly congenital forms) represents the most common cause of severe hypoglycemia leading to seizures. 1, 2
Primary Etiologic Categories
Diabetes-Related Causes
- Insulin excess from overdose, incorrect dosing, or medication errors is the predominant cause in children with known diabetes 1, 3
- Insulin-induced hypoglycemia accounts for the majority of hypoglycemic emergencies requiring intervention in diabetic children 1
- Severe hypoglycemia with seizures occurs in 17% of pediatric type 1 diabetics at 24 weeks, with 31% experiencing at least one severe episode during childhood 3, 4
- Contributing factors include: too much insulin, too little food, delayed meals, or excessive exercise 5
- 39% of severe hypoglycemic episodes occur during sleep, making nocturnal seizures particularly common 4
Hyperinsulinism (Non-Diabetic Children)
- Hyperinsulinism is the most common cause of both transient and permanent hypoglycemia disorders in infants and children without diabetes 2
- Congenital hyperinsulinism results from mutations in SUR-1, Kir6.2, glucokinase, glutamate dehydrogenase, short-chain 3-hydroxyacyl-CoA dehydrogenase, or ectopic expression of SLC16A1 2
- Perinatal stress-related hyperinsulinism occurs with birth asphyxia, maternal toxemia, prematurity, or intrauterine growth retardation 2
- Status epilepticus occurs earlier (mean 1.4 days) than brief neonatal seizures (4.3 days) in hyperinsulinemic infants 6
Metabolic and Endocrine Disorders
- Glycogen storage diseases (particularly Type I and III) present with hypoglycemia, elevated liver enzymes, and hepatomegaly 5, 1
- Fatty acid oxidation defects manifest with hypoketotic hypoglycemia 1, 6
- Hypopituitarism causes persistent hypoglycemia in neonates and requires consideration with hereditary hepatic enzyme deficiencies 7
- Ketotic hypoglycemia is the most common cause of hypoglycemia in childhood outside the neonatal period 7
Medication-Induced Causes
- Sulfonylureas and other insulin secretagogues are the most important non-insulin agents causing hypoglycemia 5
- Beta-blockers mask hypoglycemic symptoms and should be avoided in children with glycogen storage diseases 5
- Alcohol predisposes individuals to hypoglycemia 5
Infection-Related Causes
- Severe malaria may precipitate hypoglycemic seizures or posturing in endemic areas 1
- Any intercurrent illness causing prolonged fasting can trigger hypoglycemia in susceptible children 5
Critical Diagnostic Approach
Immediate Sample Collection
Before treating hypoglycemia (if the child is stable enough), draw critical diagnostic samples including: 1, 8
- Blood glucose, insulin, cortisol, growth hormone
- Lactate, free fatty acids, beta-hydroxybutyrate, acetoacetate
- Liver function tests, ammonia
- Urine for ketones and organic acids
However, never delay glucose administration if the child is symptomatic or glucose <50 mg/dL, as brain injury prevention takes absolute priority 8
Key Diagnostic Features
- Ketone status distinguishes hyperinsulinism (suppressed ketones) from fatty acid oxidation defects (hypoketotic) and ketotic hypoglycemia 1, 8, 7
- Elevated liver enzymes with normal ultrasound strongly suggests glycogen storage disease 8
- Glucagon response test (0.03 mg/kg, max 1 mg) helps diagnose GSD III 8
Age-Specific Vulnerabilities
Neonates and Young Children
- Children younger than 5-7 years have immature counterregulatory mechanisms and lack cognitive capacity to recognize hypoglycemic symptoms 1
- Young children are at risk for permanent cognitive impairment after severe hypoglycemic seizures 1
- Brief neonatal hyperinsulinemic hypoglycemic seizures have characteristics of idiopathic neonatal seizures 6
Older Children with Diabetes
- Hypoglycemia unawareness develops after repeated episodes due to defective counterregulation with failure of adrenergic responses 1
- Children with longer diabetes duration and younger age at first episode are at higher risk 4
- Lower HbA1c concentrations correlate with increased severe hypoglycemia risk 4
High-Risk Clinical Scenarios
Recurrent Severe Hypoglycemia
- Children with recurrent severe hypoglycemic seizures require psychiatric evaluation for depression, eating disorders, and intentional insulin omission 1
- Recurrent status epilepticus often follows initial status epilepticus and is frequently triggered by fever 6
Epilepsy Development
- Epilepsy develops in 21% of children following hypoglycemic seizures 6
- Epilepsy onset is shorter (1.9 months) when associated with grey matter lesions versus white matter damage (3.3 years) 6
- Epilepsy following brief neonatal seizures may be idiopathic in hyperinsulinism cases, suggesting shared genetic background 6
Critical Pitfalls to Avoid
Diagnostic Errors
- Do not assume normal liver ultrasound excludes metabolic liver disease—glycogen storage diseases cause functional abnormalities initially, with fibrosis and adenomas developing over years 5, 8
- Do not rely on bedtime glucose levels to predict nocturnal hypoglycemia, as they are poor predictors of overnight episodes 1
- Do not overlook hypoglycemia in children presenting with seizures in malaria-endemic areas 1
Management Errors
- Prehospital hypoglycemia in pediatric seizures is extremely rare (0.5%), making universal field glucose testing of low utility 9
- Glucagon should be available in homes of diabetic children, but it was available in only 80 of 97 homes and used in only 30 despite universal teaching 4
- Estrogen-containing contraceptives should be avoided in glycogen storage diseases due to hepatocellular tumor risk 5