Approach to Hypoglycemia

1. APPROACH TO HYPOGLYCEMIA IN
INFANTS AND CHILDREN

2. History:
Age of onset Neonatal period or the first two years of life – IMD
congenital hormonal deficiencies
2 year to early childhood--- ketotic hypoglycemia /
endocrine disorders
Toddlers ---- ingestion
Symptoms of hypoglycemia lethargy, irritability, uncharacteristic behaviour,
hypothermia, confusion, coma, seizures
Dietary history, fasting/illness and relationship to food Milk products ----(galactosaemia)
Fructose eg juices---- (hereditary fructose
intolerance)
Protein-----(amino acid or organic acid disorders)
Past history Neonatal history of hypoglycaemia---- (IMD)
Episodes suggestive of hypoglycaemia eg
undiagnosed seizure disorder
Family history Consanguinity
Unexplained infant deaths (inborn errors of
metabolism)
Hormonal deficiencies and hyperinsulinism

3. Examination:
Height and weight Short stature --- growth hormone deficiency/ hypopituitrism
Failure to thrive Disorders of aminoacids , organic acids and carbohydrate
metabolism. (FAO defects usually have normal weight)
Hepatomegaly glycogen storage disease, defects in gluconeogenesis,
galactosemia, or hereditary fructose intolerance
Cataract Galactosemia, congenital disorders of glycosylation
Macrosomia, hepatosplenomegaly, and umbilical hernia Beckwith-Wiedemann syndrome
Dysmorphic features Congenital dsorders of glycosylation
Macroglossia GSD 2 (pompe’s)
Dystonia / extrapyramidal symptoms Gaucher’s, orgaic academias
Midline facial defects Hypopituitarism
Ichthyosis Gaucher’s disease type2

4. Causes:
Disorders of glycogenolysis (GSDS) Glycogen synthetase deficiency
Glucose-6-phosphatase deficiency
Debrancher deficiency
Hepatic phosphorylase deficiency
Hepatic phosphorylase B kinase deficiency
Disorders of glycosylation Congenital disorders of glycosylation
Disorders of gluconeogenesis Fructose 1,6 bisphosphatase deficiency
Pyruvate carboxylase deficiency
PEPCK deficiency
Galactosemia
Hereditary fructose intolerance
Disorders of amino acid metabolism Propionic academia
Methylmalonic aciduria
Glutaric aciduria type 1
Disorders of fatty acid metabolism Medium-chain acyl-CoA dehydrogenase (MCAD) and others
Increased utilization of glucose Hyperinsulinemia
Miscellaneous Non ketotic hypoglycemia
Hormone deficiencies
Critical illness
Ingestion of oral hypoglycemics

5. Investigation:
If the cause of the hypoglycemia is unknown, the following tests should be performed on
“critical samples" collected during a period of hypoglycemia.
• Glucose
• Ketones
• Lactate
• Free fatty acids
• Carnitine / acylcarnitine
• Ammonia
• Cortisol
• Insulin/ c-peptide
• Growth hormone
• Aminoacids

6. Interpretation of critical samples:
Test Interpretation
Glucose <2.6 mmol/L - hypoglycaemia
Ketones
(Beta hydroxybutyrate )
↓ in:
•Fatty acid oxidation defect
•Hyperinsulinaemia
Lactate ↑ in:
•Metabolic liver disease
•Glycogen storage disorders
•Sepsis
•Prolonged convulsion
Free fatty acids Fatty acid oxidation defect
Carnitine / acylcarnitine Fatty acid oxidation defect
↑ in:
•Organic acidaemias
•Tyrosinaemia
•Liver dysfunction
•Hyperinsulinism-Hyperammonaemia Syndrome

7. Ammonia ↑ in:
•Organic acidaemias
•Tyrosinaemia
•Liver dysfunction
•Hyperinsulinism-Hyperammonaemia Syndrome
Cortisol ↓ in:
•Hypoadrenalism
•Hypopituitarism
•ACTH deficiency
Insulin & C-peptide Any detectable insulin in the presence of a BGL <2.6 mmol/L is
inappropriate
Growth hormone ↓ in:
•GH deficiency
•Panhypopituitarism
Amino acids Amino acid disorders

8. Clinical and laboratory features of hepatic enzyme deficiencies of glycogen/glucose metabolism in children
Enzyme deficiency Lactic acid Uric acid Serum lipids Clinical features
Glycogen synthase (GSD 0) ↑* ↑ ↑
Normal liver size
Neonatal onset
Severe fasting hypoglycemia, but
postprandial hyperglycemia and
lactic acidosis
Glucose-6-phosphatase (GSD I) ↑ ↑ ↑
Hepatomegaly
Neonatal onset
Severe fasting hypoglycemia
Some patients have neutropenia,
platelet dysfunction, renal
disease or hypertension
Glycogen debrancher (GSD III) Normal or ↑ Normal Normal or ↑
Hepatomegaly
Onset in infancy
Mild fasting hypoglycemia
May have cardiac or skeletal
muscle manifestations (eg,
elevated CK)
May have elevated RBC glycogen
Hepatic phosphorylase (GSD VI) Normal Normal Normal or ↑
Hepatomegaly
Onset in early childhood
Mild fasting hypoglycemia
Hepatic phosphorylase b kinase Normal Normal or ↑ Normal or ↑
Hepatomegaly
Onset in early childhood
Mild fasting hypoglycemia
X-linked inheritance

9. Clinical and laboratory features of hepatic enzyme deficiencies of gluconeogenesis in children:
Enzyme deficiency Lactic acid Uric acid Serum lipids Comment
G6P ↑ ↑ ↑
Hepatomegaly
Neonatal onset
Severe fasting hypoglycemia
Some patients have neutropenia,
platelet dysfunction, renal disease
or hypertension
F16DP ↑ ↑ ↑
Mild/moderate hepatomegaly
Moderate hypoglycemia
Onset in infancy
Muscular weakness
Failure to thrive
Hyperalaninemia
PEPCK ↑ Normal ↑
Onset in infancy
Severe hypoglycemia
Elevated transaminases
Coagulation abnormalities
Fatty liver, fatty kidneys
PC ↑ Normal Normal or ↑
Onset in infancy, with early death
Mild hypoglycemia
Severe mental retardation
Subacute necrotizing
encephalopathy

11. THANK YOU