Clinical Scenario:
A 5-day-old full-term male neonate with a birth weight of 4.7 kg develops recurrent episodes of jitteriness and poor feeding despite receiving adequate enteral nutrition. His capillary blood glucose is repeatedly between 25–35 mg/dL. To maintain normoglycemia, he requires a glucose infusion rate of 14 mg/kg/min. A critical blood sample obtained during hypoglycemia shows an inappropriately detectable plasma insulin level, suppressed serum ketones, low free fatty acid concentrations, and normal serum cortisol and growth hormone levels.
What is the most likely diagnosis?
A. Congenital adrenal hyperplasia
B. Congenital hyperinsulinism
C. Glycogen storage disease type I
D. Medium-chain acyl-CoA dehydrogenase deficiency
E. Neonatal sepsis
Correct answer & Explanation:
Correct Answer: B. Congenital hyperinsulinism
Explanation
This neonate has the characteristic biochemical profile of congenital hyperinsulinism (CHI), the most common cause of persistent hypoglycemia in infancy.
The diagnosis is supported by:
- Macrosomia (birth weight 4.7 kg), suggesting fetal hyperinsulinism
- Persistent hypoglycemia despite adequate feeding
- Requirement for a glucose infusion rate of 14 mg/kg/min, which is well above the normal neonatal requirement (approximately 4–6 mg/kg/min) and strongly suggests hyperinsulinism
- Inappropriately detectable insulin during hypoglycemia
- Suppressed ketone production
- Low free fatty acid concentrations
- Appropriate cortisol and growth hormone responses, excluding major endocrine deficiencies
Excess insulin suppresses glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis, resulting in hypoketotic hypoglycemia.
Why the other options are incorrect
A. Congenital adrenal hyperplasia
May cause neonatal hypoglycemia due to cortisol deficiency, but insulin is appropriately suppressed, ketones are usually elevated, and electrolyte abnormalities (hyponatremia and hyperkalemia) are common.
B. Congenital hyperinsulinism
Correct. The combination of a high glucose infusion requirement, detectable insulin during hypoglycemia, suppressed ketones, and low free fatty acids is diagnostic.
C. Glycogen storage disease type I
Typically presents later in infancy with hepatomegaly, fasting hypoglycemia, hyperlactatemia, hyperuricemia, and hypertriglyceridemia.
D. Medium-chain acyl-CoA dehydrogenase deficiency
Causes hypoketotic hypoglycemia, but insulin levels are suppressed, and presentation usually follows prolonged fasting or illness rather than occurring in the first few days of life.
E. Neonatal sepsis
Can cause hypoglycemia but does not produce the characteristic metabolic profile of hyperinsulinism.
Learning Point
A neonate with persistent hypoglycemia requiring a glucose infusion rate >8 mg/kg/min, together with inappropriately detectable insulin, suppressed ketones, and low free fatty acids, should be considered to have congenital hyperinsulinism until proven otherwise.
