Subscribe to RSS
Pyridoxine Therapy: Not Just the Dose, the Duration Matters Too
Pyridoxine-dependent epilepsy (PDE) (OMIM 266100) is an autosomal recessive disorder of lysine metabolism secondary to antiquitin deficiency. The prototypical presentation is intractable neonatal seizures that do not respond to conventional antiseizure medication but are well controlled by pyridoxine supplementation. Atypical forms account for one-third of the PDE spectrum and may escape early diagnosis. The common atypical presentations include the prenatal onset of seizures, seizures onset as delayed as 3 years of age, autism, arrested hydrocephalus, and fetal ventriculomegaly. Herein, we describe a 9-month-old child with neonatal-onset refractory seizures who failed two short trials of pyridoxine therapy and was later diagnosed with PDE by molecular studies. Regardless of the therapeutic response, a prolonged course of pyridoxine therapy is justified to identify delayed responders in infants with drug-refractory epilepsy of no apparent etiology.
A.C.C. supported in patient management and writing the draft of manuscript. M.T. involved in patient management, writing the draft of manuscript, and review of literature. R.G. and T.S. dedicated in patient management, critical review of manuscript for important intellectual content, and final approval of the version to be published. T.S. performed as guarantor for the paper. A.K. contributed as a clinician in charge, conceived the concept of study, and carried out the critical review of manuscript for important intellectual content. T.S. cooperated in patient management, critical review of manuscript for important intellectual content, and final approval of the version to be published.
An informed consent form was signed by the parents of the patient to approve the use of patient information or material for scientific purposes. The patient identity has not been disclosed anywhere in the manuscript and does not contain any identifiable images.
Received: 06 September 2020
Accepted: 12 October 2020
Article published online:
07 December 2020
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 Stockler S, Plecko B, Gospe Jr SM. et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab 2011; 104 (1-2): 48-60
- 2 Hunt Jr AD, Stokes Jr J, McCRORY WW, Stroud HH. Pyridoxine dependency: report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics 1954; 13 (02) 140-145
- 3 Mills PB, Struys E, Jakobs C. et al. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med 2006; 12 (03) 307-309
- 4 van Karnebeek CD, Tiebout SA, Niermeijer J. et al. Pyridoxine-dependent epilepsy: an expanding clinical spectrum. Pediatr Neurol 2016; 59: 6-12
- 5 Plecko B. Pyridoxine and Pyridoxalphosphate-Dependent Epilepsies: Handbook of Clinical Neurology. Elsevier; 2013. p. 1811–1817. Available at: https://linkinghub.elsevier.com/retrieve/pii/B9780444595652000502.
- 6 Srinivasaraghavan R, Parameswaran N, Mathis D, Bürer C, Plecko B. Antiquitin deficiency with adolescent onset epilepsy: molecular diagnosis in a mother of affected offsprings. Neuropediatrics 2018; 49 (02) 154-157
- 7 Bass NE, Wyllie E, Cohen B, Joseph SA. Pyridoxine-dependent epilepsy: the need for repeated pyridoxine trials and the risk of severe electrocerebral suppression with intravenous pyridoxine infusion. J Child Neurol 1996; 11 (05) 422-424
- 8 van Karnebeek CDM, Jaggumantri S. Current treatment and management of pyridoxine-dependent epilepsy. Curr Treat Options Neurol 2015; 17 (02) 335
- 9 Mills PB, Footitt EJ, Mills KA. et al. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency). Brain 2010; 133 (Pt 7): 2148-2159
- 10 Plecko B, Paul K, Paschke E. et al. Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene. Hum Mutat 2007; 28 (01) 19-26
- 11 Gallagher RC, Van Hove JLK, Scharer G. et al. Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy. Ann Neurol 2009; 65 (05) 550-556
- 12 Grillo E, da Silva RJ, Barbato Jr JH. Pyridoxine-dependent seizures responding to extremely low-dose pyridoxine. Dev Med Child Neurol 2001; 43 (06) 413-415
- 13 Coughlin II CR, Swanson MA, Spector E. et al. The genotypic spectrum of ALDH7A1 mutations resulting in pyridoxine dependent epilepsy: a common epileptic encephalopathy. J Inherit Metab Dis 2019; 42 (02) 353-361
- 14 Bok LA, Maurits NM, Willemsen MA. et al. The EEG response to pyridoxine-IV neither identifies nor excludes pyridoxine-dependent epilepsy. Epilepsia 2010; 51 (12) 2406-2411