Approach to Hypoglycemia in Pediatric Metabolic Liver Diseases: A Clinical Overview

Review ARticlehyperinsulinism, though it is occasionally seen in mitochondrial defects (e.g., MPV17) and after fructose ingestion in HFI.In galactosemia, hypoglycemia is precipitated by a galactose load, which is milk in a neonate.Those on galactose-free (e.g., soy) formula from birth will not manifest.In GSD I, hypoglycemia occurs after a brief fast (1.5-4 hours), once exogenous sources of glucose are exhausted.Hypoglycemia occurs later in other GSDs (4-12 hours) and in disorders of gluconeogenesis (8-16 hours).FAODs typically manifest after >10 hours of fasting or earlier in a catabolic state such as febrile illness. 2 FAODs typically present as hypoketotic hypoglycemia, whereas other causes are normo-or hyperketotic.2 PathoPhysiology Metabolic liver diseases interfere with one or more of the liver's energy-regulating 5 processes:• Glycogenolysis/gluconeogenesis: In hepatic GSD (types I, III, VI, IX), enzyme deficiencies block glycogen breakdown or glucose release, causing ketotic hypoglycemia.• Fatty acid oxidation: FAODs impair mitochondrial beta-oxidation, resulting in nonketotic hypoglycemia during fasting due to an inability to generate ketones.• Hepatocellular dysfunction: Galactosemia and tyrosinemia, accumulation of toxic metabolites, impair hepatic glucose production, and may induce liver failure.