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Pyridoxal 5'-phosphate-dependent epilepsy

Reviewed June 2008

What is pyridoxal 5'-phosphate-dependent epilepsy?

Pyridoxal 5'-phosphate-dependent epilepsy is a condition that involves seizures beginning soon after birth or, in some cases, before birth. The seizures typically involve irregular involuntary muscle contractions (myoclonus), abnormal eye movements, and convulsions. Most babies with this condition are born prematurely and may have a temporary, potentially toxic, increase in lactic acid in the blood (lactic acidosis). Additionally, some infants have a slow heart rate and a lack of oxygen during delivery (fetal distress).

Anticonvulsant drugs, which are usually given to control seizures, are ineffective in people with pyridoxal 5'-phosphate-dependent epilepsy. Instead, individuals with this type of epilepsy are medically treated with large daily doses of pyridoxal 5'-phosphate (a form of vitamin B6). If left untreated, people with this condition can develop severe brain dysfunction (encephalopathy), which can lead to death. Even though seizures can be controlled with pyridoxal 5'-phosphate, neurological problems such as developmental delay and learning disorders may still occur.

How common is pyridoxal 5'-phosphate-dependent epilepsy?

Pyridoxal 5'-phosphate-dependent epilepsy is a rare condition; approximately 14 cases have been described in the scientific literature.

What genes are related to pyridoxal 5'-phosphate-dependent epilepsy?

Mutations in the PNPO gene cause pyridoxal 5'-phosphate-dependent epilepsy. The PNPO gene provides instructions for producing an enzyme called pyridoxine 5'-phosphate oxidase. This enzyme is involved in the conversion (metabolism) of vitamin B6 derived from food (in the form of pyridoxine and pyridoxamine) to the active form of vitamin B6 called pyridoxal 5'-phosphate (PLP). PLP is necessary for many processes in the body including protein metabolism and the production of chemicals that transmit signals in the brain (neurotransmitters).

PNPO gene mutations result in a pyridoxine 5'-phosphate oxidase enzyme that is unable to metabolize pyridoxine and pyridoxamine, leading to a deficiency of PLP. A shortage of PLP can disrupt the function of many other proteins and enzymes that need PLP in order to be effective. It is not clear how the lack of PLP affects the brain and leads to the seizures that are characteristic of pyridoxal 5'-phosphate-dependent epilepsy.

Related Gene(s)

Changes in this gene are associated with pyridoxal 5'-phosphate-dependent epilepsy.

  • PNPO

How do people inherit pyridoxal 5'-phosphate-dependent epilepsy?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of pyridoxal 5'-phosphate-dependent epilepsy?

These resources address the diagnosis or management of pyridoxal 5'-phosphate-dependent epilepsy and may include treatment providers.

  • Genetic Testing Registry: Pyridoxal 5'-phosphate-dependent epilepsy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1864723)
  • MedlinePlus Encyclopedia: Lactic acidosis (http://www.nlm.nih.gov/medlineplus/ency/article/000391.htm)

You might also find information on the diagnosis or management of pyridoxal 5'-phosphate-dependent epilepsy in Educational resources (http://www.ghr.nlm.nih.gov/condition/pyridoxal-5-phosphate-dependent-epilepsy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/pyridoxal-5-phosphate-dependent-epilepsy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about pyridoxal 5'-phosphate-dependent epilepsy?

You may find the following resources about pyridoxal 5'-phosphate-dependent epilepsy helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Drugs and Supplements: Vitamin B6 (http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-b6.html)
    • Encyclopedia: Lactic acidosis (http://www.nlm.nih.gov/medlineplus/ency/article/000391.htm)
    • Health Topic: Epilepsy (http://www.nlm.nih.gov/medlineplus/epilepsy.html)
    • Health Topic: Seizures (http://www.nlm.nih.gov/medlineplus/seizures.html)

  • Additional NIH Resources - National Institutes of Health

    • National Institute of Neurological Disorders and Stroke: Epilepsy Information Page (http://www.ninds.nih.gov/disorders/epilepsy/epilepsy.htm)
    • National Institute of Neurological Disorders and Stroke: Myoclonus Fact Sheet (http://www.ninds.nih.gov/disorders/myoclonus/detail_myoclonus.htm)

  • Educational resources - Information pages

    • Children's Hospital Boston: Seizures and Epilepsy (http://www.childrenshospital.org/az/Site1967/mainpageS1967P0.html)
    • Merck Manual Home Edition for Patients and Caregivers: Seizure Disorders (http://www.merckmanuals.com/home/brain_spinal_cord_and_nerve_disorders/seizure_disorders/seizure_disorders.html)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=79096)

  • Patient support - For patients and families

    • American Epilepsy Society (http://www.aesnet.org/)
    • Epilepsy Foundation (http://www.epilepsyfoundation.org/)
    • Family Village (http://www.familyvillage.wisc.edu/lib_epil.htm)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Genetic Testing Registry - Repository of genetic test information

    • Genetic Testing Registry: Pyridoxal 5'-phosphate-dependent epilepsy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1864723)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22Epilepsy%22%20OR%20%22pyridoxal%205%27-phosphate-dependent%20epilepsy%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((pyridoxal%205'-phosphate%20dependent%20epilepsy)%20OR%20(pyridoxine%205'-phosphate%20oxidase%20deficiency))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/610090)

What other names do people use for pyridoxal 5'-phosphate-dependent epilepsy?

  • PNPO Deficiency
  • PNPO-Related Neonatal Epileptic Encephalopathy
  • pyridoxamine 5-prime-phosphate oxidase deficiency
  • pyridoxine-5'-phosphate oxidase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about pyridoxal 5'-phosphate-dependent epilepsy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding pyridoxal 5'-phosphate-dependent epilepsy?

acidosis ; autosomal ; autosomal recessive ; cell ; deficiency ; developmental delay ; encephalopathy ; enzyme ; gene ; involuntary ; lactic acid ; lactic acidosis ; metabolism ; myoclonus ; neonatal ; neurological ; neurotransmitters ; oxidase ; oxygen ; phosphate ; protein ; recessive ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bagci S, Zschocke J, Hoffmann GF, Bast T, Klepper J, Müller A, Heep A, Bartmann P, Franz AR. Pyridoxal phosphate-dependent neonatal epileptic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2008 Mar;93(2):F151-2. doi: 10.1136/adc.2006.115162. (http://www.ncbi.nlm.nih.gov/pubmed/18296573?dopt=Abstract)
  • Hoffmann GF, Schmitt B, Windfuhr M, Wagner N, Strehl H, Bagci S, Franz AR, Mills PB, Clayton PT, Baumgartner MR, Steinmann B, Bast T, Wolf NI, Zschocke J. Pyridoxal 5'-phosphate may be curative in early-onset epileptic encephalopathy. J Inherit Metab Dis. 2007 Feb;30(1):96-9. Epub 2006 Dec 23. (http://www.ncbi.nlm.nih.gov/pubmed/17216302?dopt=Abstract)
  • Hoffmann GF, Schmitt B, Windfuhr M, Wagner N, Strehl H, Bagci S, Franz AR, Mills PB, Clayton PT, Baumgartner MR, Steinmann B, Bast T, Wolf NI, Zschocke J. Pyridoxal 5'-phosphate may be curative in early-onset epileptic encephalopathy. J Inherit Metab Dis. 2007 Feb;30(1):96-9. Epub 2006 Dec 23. (http://www.ncbi.nlm.nih.gov/pubmed/17216302?dopt=Abstract)
  • Khayat M, Korman SH, Frankel P, Weintraub Z, Hershckowitz S, Sheffer VF, Ben Elisha M, Wevers RA, Falik-Zaccai TC. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism. Mol Genet Metab. 2008 Aug;94(4):431-4. doi: 10.1016/j.ymgme.2008.04.008. Epub 2008 May 15. (http://www.ncbi.nlm.nih.gov/pubmed/18485777?dopt=Abstract)
  • Mills PB, Surtees RA, Champion MP, Beesley CE, Dalton N, Scambler PJ, Heales SJ, Briddon A, Scheimberg I, Hoffmann GF, Zschocke J, Clayton PT. Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. Hum Mol Genet. 2005 Apr 15;14(8):1077-86. Epub 2005 Mar 16. (http://www.ncbi.nlm.nih.gov/pubmed/15772097?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2008
Published: May 20, 2013