Laboratory Studies

See the list below:

Perform hematology tests, a sepsis screen, and metabolic (profile) tests.
Plecko et al have confirmed pipecolic acid (PA) levels are elevated in the plasma of patients with pyridoxine (vitamin B-6)–dependent seizure (PDS) both before and after treatment with pyridoxine.^[21]Furthermore, alpha amino adipic semialdehyde (AASA) levels are also elevated in plasma, urine, and cerebrospinal fluid (CSF).^[24]They have recommended PA and AASA levels in plasma and urine be used as markers to select for patients who need molecular analysis of the antiquitin gene.^[23]

Imaging Studies

See the list below:

Despite several reports about imaging studies, no typical abnormality has been found in PDS.^{[1, 2]}
A high prevalence of structural CNS defects has been reported, as well as varying degrees of grey and white matter atrophy, thinning of the corpus callosum, and the presence of mega cisterna magna.^[1]
Progressive cortical-white matter atrophy and ventricular dilation is also present in inadequately treated patients with PDS.^{[1, 2]}
Hydrocephalus of unknown origin can also occur.
Baxter reports apparent cysts adjacent to the lateral ventricles in some neonatal-onset ultrasonographic images.
CT scanning and MRI reveal structural abnormalities in the brain in addition to white matter abnormalities.^[2]
CT scanning and MRI do not have a well-established role in the diagnosis of PDS.^[1]

Other Tests

See the list below:

Following pyridoxine administration, the EEG usually takes 2-6 minutes to normalize. The pattern is typically suggestive of diffuse and focal dysfunction and may show focal discharges; however, some EEG patterns have been normal (ie, bursts or runs of high-voltage, relatively bilateral synchronous sharp and slow [1-4 Hz] wave activity [either ictally or interictally]).^[1]
EEG does not have a well-established role in the diagnosis of PDS. One report suggests that the abnormal EEG is a result of the administration of anticonvulsants to the patient prior to the diagnosis of PDS.^[19]
Two case studies by Cirillo et al present the difficulties in diagnosing pyridoxine-dependent seizures by using EEG response to pyridoxine treatment. One patient who was later diagnosed with PDS had no EEG changes while another patient who had extreme EEG changes was not diagnosed with PDS. The study recommended the continuation of oral pyridoxine treatment until laboratory testing confirms the diagnosis.^[25]

Procedures

See the list below:

Perform a CSF examination (ie, lumbar puncture).

Treatment & Management

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Demirbilek H, Alanay Y, Alikasifoglu A, Topçu M, Mornet E, Gönç N, et al. Hypophosphatasia presenting with pyridoxine-responsive seizures, hypercalcemia, and pseudotumor cerebri: case report. J Clin Res Pediatr Endocrinol. 2012 Mar. 4(1):34-8. [Medline]. [Full Text].
Belachew D, Kazmerski T, Libman I, Goldstein AC, Stevens ST, Deward S, et al. Infantile hypophosphatasia secondary to a novel compound heterozygous mutation presenting with pyridoxine-responsive seizures. JIMD Rep. 2013. 11:17-24. [Medline]. [Full Text].
Hunt AD Jr, Stokes J Jr, McCrory WW, Stroud HH. Pyridoxine dependency: report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics. 1954 Feb. 13(2):140-5. [Medline].
Burd L, Stenehjem A, Franceschini LA, Kerbeshian J. A 15-year follow-up of a boy with pyridoxine (vitamin B6)-dependent seizures with autism, breath holding, and severe mental retardation. J Child Neurol. 2000 Nov. 15(11):763-5. [Medline].
Grillo E, da Silva RJ, Barbato JH Jr. Pyridoxine-dependent seizures responding to extremely low-dose pyridoxine. Dev Med Child Neurol. 2001 Jun. 43(6):413-5. [Medline].
Bahi-Buisson N, Dulac O. Epilepsy in inborn errors of metabolism. Handb Clin Neurol. 2013. 111:533-41. [Medline].
Kuo MF, Wang HS. Pyridoxal phosphate-responsive epilepsy with resistance to pyridoxine. Pediatr Neurol. 2002 Feb. 26(2):146-7. [Medline].
Kure S, Sakata Y, Miyabayashi S, et al. Mutation and polymorphic marker analyses of 65K- and 67K-glutamate decarboxylase genes in two families with pyridoxine-dependent epilepsy. J Hum Genet. 1998. 43(2):128-31. [Medline].
Battaglioli G, Rosen DR, Gospe SM Jr, Martin DL. Glutamate decarboxylase is not genetically linked to pyridoxine-dependent seizures. Neurology. 2000 Jul 25. 55(2):309-11. [Medline].
Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, et al. Mutations in antiquitin in individuals with pyridoxinedependent seizures. Nat Med. 2006. 12:307–9. And 14.
Bennett CL, Chen Y, Hahn S, Glass IA, Gospe Jr SM. Prevalence of ALDH7A1 mutations in 18 North American pyridoxinedependent seizure (PDS) patients. Epilepsia. 2009. 50:1167–75.
S.M. Gospe Jr. Neonatal vitamin-responsive epileptic encephalopathies. Chang Gung Med J. 2010. 33:1–12.
Been JV, Bok LA, Andriessen P, Renier WO. Epidemiology of pyridoxine dependent seizures in the Netherlands. Arch Dis Child. 2005 Dec. 90(12):1293-6. [Medline].
Baxter P. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK. Arch Dis Child. 1999 Nov. 81(5):431-3. [Medline].
Baxter P. Pyridoxine dependent epilepsy: a suggestive electroclinical pattern. Arch Dis Child Fetal Neonatal Ed. 2000 Sep. 83(2):F163. [Medline].
N.S. Yeghiazaryan, P. Striano, L. Spaccini et al. Long-term follow-up in two siblings with pyridoxine-dependent seizures associated with a novel ALDH7A1 mutation. Eur J Paediatr Neurol. 2011. 15:547–550.
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 Jan. 28(1):19-26. [Medline].
Kanno J, Kure S, Narisawa A, et al. Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed by ALDH7A1 mutational analysis. Mol Genet Metab. 2007 Aug. 91(4):384-9. [Medline].
Stockler S, Plecko B, Gospe SM Jr, Coulter-Mackie M, Connolly M, van Karnebeek C, et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab. 2011 Sep-Oct. 104(1-2):48-60. [Medline].
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Author

Haritha Reddy Chelimilla, MD Fellow, Department of Gastroenterology, Bronx-Lebanon Hospital Center

Haritha Reddy Chelimilla, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Medical Association, Medical Society of the State of New York, Indian Medical Association, New York Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Coauthor(s)

Suresh Kumar Nayudu, MD Fellow in Gastroenterology, Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine of Yeshiva University

Suresh Kumar Nayudu, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Medical Society of the State of New York, American Association of Physicians of Indian Origin, Americas Hepato-Pancreato-Biliary Association

Disclosure: Nothing to disclose.

Prospere Remy, MD Assistant Professor of Medicine, Albert Einstein College of Medicine; Attending Physician, Department of Internal Medicine, Bronx-Lebanon Hospital Center

Prospere Remy, MD is a member of the following medical societies: American College of Physicians, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Jatinder Bhatia, MBBS, FAAP Professor of Pediatrics, Medical College of Georgia, Georgia Regents University; Chief, Division of Neonatology, Director, Fellowship Program in Neonatal-Perinatal Medicine, Director, Transport/ECMO/Nutrition, Vice Chair, Clinical Research, Department of Pediatrics, Children's Hospital of Georgia

Jatinder Bhatia, MBBS, FAAP is a member of the following medical societies: Academy of Nutrition and Dietetics, American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Society for Nutrition, American Society for Parenteral and Enteral Nutrition, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Nestle<br/>Serve(d) as a speaker or a member of a speakers bureau for: Nestle<br/>Received income in an amount equal to or greater than $250 from: Nestle.

Chief Editor

Additional Contributors

Steven M Schwarz, MD, FAAP, FACN, AGAF Professor of Pediatrics, Children's Hospital at Downstate, State University of New York Downstate Medical Center

Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American Association for Physician Leadership, New York Academy of Medicine, Gastroenterology Research Group, American Gastroenterological Association, American Pediatric Society, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Michael D Nissen, MBBS, FRACP, FRCPA Associate Professor in Biomolecular, Biomedical Science & Health, Griffith University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert Sakzewski Viral Research Centre, Royal Children's Hospital

Disclosure: Nothing to disclose.

Catherine O'Neil, BHlthSc, APD Clinical Dietician/Nutritionist, Royal Children's Hospital, Australia; Community Nutritionist, Save the Children Fund

Disclosure: Nothing to disclose.

Anjali Parish, MD Assistant Professor of Pediatrics, Department of Neonatology, Medical College of Georgia

Anjali Parish, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association

Disclosure: Nothing to disclose.

Judith A Wilcox Director of Nutrition and Dietetics, Royal Children's Hospital, Australia

Disclosure: Nothing to disclose.