Udo Fg Engelke, Rianne E van Outersterp, Jona Merx, Fred Amg van Geenen, Arno van Rooij, Giel Berden, Marleen Cdg Huigen, Leo Aj Kluijtmans, Tessa Ma Peters, Hilal H Al-Shekaili, Blair R Leavitt, Erik de Vrieze, Sanne Broekman, Erwin van Wijk, Laura A Tseng, Purva Kulkarni, Floris Pjt Rutjes, Jasmin Mecinovic, Eduard A Struys, Laura A Jansen, Sidney M Gospe, Saadet Mercimek-Andrews, Keith Hyland, Michel Aap Willemsen, Levinus A Bok, Clara Dm Van Karnebeek, Ron A Wevers, Thomas J Boltje, Jos Oomens, Jonathan Martens, Karlien Lm Coene
Pyridoxine-dependent epilepsy (PDE-ALDH7A1), also known as antiquitin deficiency, is an inborn error of lysine metabolism that presents with refractory epilepsy in newborns. Bi-allelic ALDH7A1 variants lead to deficiency of α-aminoadipic semialdehyde dehydrogenase, resulting in accumulation of piperideine-6-carboxylate (P6C), and secondary deficiency of the important co-factor pyridoxal-5'-phosphate (PLP, active vitamin B6) through its complexation with P6C. Vitamin B6 supplementation resolves epilepsy in patients, but despite this treatment, intellectual disability may occur...
June 17, 2021: Journal of Clinical Investigation