Pyridoxine dependent epilepsy (PDE) was first described by Hunt in 1954. In 1969, Dr Scriver suggested that PDE was caused by reduced binding of pyridoxal phosphate to glutamate decarboxylase leading to buildup of excitotoxic glutamate and deficiency of inhibitory GABA in the brain.
In 2005, a group identified the gene ALDH7A1 encoding antiquitin (P6C-alpha-AASA dehydrogenase) as the culprit in PDE. This astute discovery was made following the report of pipecolic acid accumulation in PDE and by hypothesizing that P6C inactivates pyridoxal phosphate in a similar fashion as P5C in hyperprolinemia type II.
Nat Med. 2006 Mar;12(3):307-9. Epub 2006 Feb 19.
Mutations in antiquitin in individuals with pyridoxine-dependent seizures.
Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA,
Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT.
For great reviews, see:
JÂ Inherit Metab Dis. 2006 Apr;29(2-3):317-26.
B(6)-responsive disorders: A model of vitamin dependency.
OMMBID chapter 86.1.
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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator