A newborn develops seizures within the first hours of life that are refractory to phenobarbitone, phenytoin, and pyridoxine given individually, but abort completely when pyridoxine is continued as a daily maintenance dose. CSF and metabolic workup are otherwise normal. What is the underlying mechanism?
- A Accumulation of branched chain amino acids
- B Deficiency of glutamic acid decarboxylase activity due to reduced GABA synthesis ✓
- C Impaired myelination from folate trap
- D Defective carnitine transport causing fatty acid oxidation block
Correct answer: B. Deficiency of glutamic acid decarboxylase activity due to reduced GABA synthesis
Explanation
Pyridoxine dependent epilepsy arises from mutations in ALDH7B1 causing accumulation of alpha-aminoadipic semialdehyde which inactivates PLP, the cofactor for glutamic acid decarboxylase. Reduced GABA synthesis leads to neonatal seizures that respond dramatically to pharmacological doses of pyridoxine. Maple syrup urine disease elevates branched chain amino acids, and the folate trap relates to A12 deficiency, neither of which responds to pyridoxine monotherapy.
Reference: Nelson Textbook of Pediatrics, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.