Gluconeogenesis MCQ — NEET PG Practice Question | NEETPGAI
Gluconeogenesis
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flask-conical Biochemistry
A 3-year-old child presents with severe hypoglycemia (blood glucose 28 mg/dL) and hepatomegaly during a 6-hour fast. The child is lethargic and has seizure-like activity. Serum lactate is elevated at 8 mmol/L (normal <2). The parents report recurrent episodes after fasting or illness. Which investigation would best confirm a defect in gluconeogenesis?
A. Fasting serum insulin and C-peptide levels
B. Plasma glucose and lactate ratio after 12-hour fast with glucagon stimulation test
C. Liver biopsy with enzyme assay for glucose-6-phosphatase activity
D. Urine organic acids and plasma amino acid profile
Explanation
Diagnostic Approach to Gluconeogenesis Defects
Clinical Context
This child presents with fasting hypoglycemia with lactic acidosis — a hallmark pattern of gluconeogenesis impairment. The elevated lactate and normal/low insulin (implying the liver cannot respond to hypoglycemia) point to a hepatic enzyme defect rather than insulin excess.
Why Glucagon Stimulation Test?
Key Point
The glucagon stimulation test (or prolonged fast with glucagon challenge) is the gold standard screening investigation for gluconeogenesis defects because:
1.
Glucagon bypasses insulin-mediated pathways — it directly activates hepatic glycogenolysis and gluconeogenesis via cAMP
2.
Failure to raise glucose despite glucagon = hepatic glucose output defect (gluconeogenesis or glycogenolysis impairment)
3.
Lactate rises further = substrate (pyruvate/lactate) accumulates because it cannot be converted to glucose
4.
Glucose-to-lactate ratio becomes diagnostic — in gluconeogenesis defects, this ratio is typically <3 (normal >5)
Interpretation Table
Table
Finding
Normal Response
Gluconeogenesis Defect
Glucose after glucagon
Rises >30 mg/dL
Minimal rise (<10 mg/dL)
Lactate after glucagon
Unchanged or ↓
Rises further
Glucose:Lactate ratio
>5
<3
Insulin level
Suppressed (<2 mIU/L)
Suppressed
High-YieldNEET PG
The lactate paradox — lactate rises when glucose should rise — is pathognomonic for gluconeogenesis defects (especially PEPCK, FBPase-1, or G6Pase deficiency).
Why Not the Other Options?
Liver biopsy with enzyme assay (Option B):
Invasive and not first-line screening
Requires specialized histochemistry; not available in all centers
Reserved for confirmation after biochemical testing
Useful for identifying organic acidemias (e.g., methylmalonic aciduria, propionic acidemia)
These cause lactic acidosis via different mechanisms (impaired pyruvate oxidation)
Not specific for gluconeogenesis defects
Fasting insulin & C-peptide (Option D):
Rules out hyperinsulinemic hypoglycemia (opposite problem)
In gluconeogenesis defects, insulin is appropriately suppressed — the defect is not insulin-mediated
Does not confirm the specific hepatic enzyme defect
Clinical Pearl
Gluconeogenesis defects (PEPCK, FBPase-1, G6Pase deficiency) present with fasting hypoglycemia + lactic acidosis + hepatomegaly. The glucagon stimulation test distinguishes these from glycogen storage diseases (which respond to glucagon) and hyperinsulinemic hypoglycemia (which have elevated insulin).
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