Pyridoxine-dependent epilepsy

Reviewed February 2013

What is pyridoxine-dependent epilepsy?

Pyridoxine-dependent epilepsy is a condition that involves seizures beginning in infancy or, in some cases, before birth. Those affected typically experience prolonged seizures lasting several minutes (status epilepticus). These seizures involve muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures). Additional features of pyridoxine-dependent epilepsy include low body temperature (hypothermia), poor muscle tone (dystonia) soon after birth, and irritability before a seizure episode. In rare instances, children with this condition do not have seizures until they are 1 to 3 years old.

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

How common is pyridoxine-dependent epilepsy?

Pyridoxine-dependent epilepsy occurs in 1 in 100,000 to 700,000 individuals. At least 100 cases have been reported worldwide.

What genes are related to pyridoxine-dependent epilepsy?

Mutations in the ALDH7A1 gene cause pyridoxine-dependent epilepsy. The ALDH7A1 gene provides instructions for making an enzyme called α-aminoadipic semialdehyde (α-AASA) dehydrogenase, also known as antiquitin. This enzyme is involved in the breakdown of the protein building block (amino acid) lysine in the brain.

When antiquitin is deficient, a molecule that interferes with vitamin B6 function builds up in various tissues. Pyridoxine plays a role in many processes in the body, such as the breakdown of amino acids and the productions of chemicals that transmit signals in the brain (neurotransmitters). It is unclear how a lack of pyridoxine causes the seizures that are characteristic of this condition.

Some individuals with pyridoxine-dependent epilepsy do not have identified mutations in the ALDH7A1 gene. In these cases, the cause of the condition is unknown.

Related Gene(s)

Changes in this gene are associated with pyridoxine-dependent epilepsy.

ALDH7A1

How do people inherit pyridoxine-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 pyridoxine-dependent epilepsy?

These resources address the diagnosis or management of pyridoxine-dependent epilepsy and may include treatment providers.

Gene Review: Pyridoxine-Dependent Epilepsy (http://www.ncbi.nlm.nih.gov/books/NBK1486/)
Genetic Testing Registry: Pyridoxine-dependent epilepsy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1849508)
MedlinePlus Encyclopedia: Generalized tonic-clonic seizure (http://www.nlm.nih.gov/medlineplus/ency/article/000695.htm)

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

You may find the following resources about pyridoxine-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: Generalized tonic-clonic seizure (http://www.nlm.nih.gov/medlineplus/ency/article/000695.htm)
- Health Topic: Epilepsy (http://www.nlm.nih.gov/medlineplus/epilepsy.html)
- Health Topic: Seizures (http://www.nlm.nih.gov/medlineplus/seizures.html)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/9298/resources/resources/1)
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)
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=3006)
- University of Washington: Pyridoxine-Dependent Seizures Registry (http://faculty.washington.edu/sgospe/pyridoxine/)
Patient support - For patients and families
- American Epilepsy Society (http://www.aesnet.org/)
- CLIMB: Children Living with Inherited Metabolic Diseases (http://www.climb.org.uk/)
- Epilepsy Foundation: Managing Status Epilepticus (http://www.epilepsyfoundation.org/livingwithepilepsy/parentsandcaregivers/parents/managing-status-epilepticus.cfm)
- Epilepsy Foundation: Status Epilepticus (http://www.epilepsyfoundation.org/aboutepilepsy/firstaid/statusepilepticus.cfm)
- Family Village (http://www.familyvillage.wisc.edu/lib_epil.htm)
- National Organization for Rare Disorders (NORD) (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1126/viewAbstract)

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

Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1486/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Pyridoxine-dependent epilepsy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1849508)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?term=%22pyridoxine-dependent%20epilepsy%22%20%5BDISEASE%5D%20OR%20%22vitamin%20B6-dependent%20seizures%22%20%5BDISEASE%5D%20OR%20NCT00552045%20%5BID-NUMBER%5D%20OR%20NCT00041600%20%5BID-NUMBER%5D)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((pyridoxine-dependent%20epilepsy%5BTIAB%5D)%20OR%20(pyridoxine-dependent%20seizures%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/266100)

What other names do people use for pyridoxine-dependent epilepsy?

AASA dehydrogenase deficiency
EPD
epilepsy, pyridoxine-dependent
PDE
Pyridoxine Dependency
pyridoxine dependency
pyridoxine dependency with seizures
pyridoxine-dependent seizures
vitamin B6-dependent seizures

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 pyridoxine-dependent epilepsy?

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

What glossary definitions help with understanding pyridoxine-dependent epilepsy?

acids ; amino acid ; autosomal ; autosomal recessive ; cell ; deficiency ; dehydrogenase ; developmental delay ; dystonia ; encephalopathy ; enzyme ; gene ; molecule ; muscle tone ; neurological ; neurotransmitters ; oxidase ; phosphate ; protein ; recessive ; seizure ; status epilepticus

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

References

Bok LA, Struys E, Willemsen MA, Been JV, Jakobs C. Pyridoxine-dependent seizures in Dutch patients: diagnosis by elevated urinary alpha-aminoadipic semialdehyde levels. Arch Dis Child. 2007 Aug;92(8):687-9. Epub 2006 Nov 6. (http://www.ncbi.nlm.nih.gov/pubmed/17088338?dopt=Abstract)
Kanno J, Kure S, Narisawa A, Kamada F, Takayanagi M, Yamamoto K, Hoshino H, Goto T, Takahashi T, Haginoya K, Tsuchiya S, Baumeister FA, Hasegawa Y, Aoki Y, Yamaguchi S, Matsubara Y. Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed by ALDH7A1 mutational analysis. Mol Genet Metab. 2007 Aug;91(4):384-9. Epub 2007 Apr 11. (http://www.ncbi.nlm.nih.gov/pubmed/17433748?dopt=Abstract)
Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA, Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med. 2006 Mar;12(3):307-9. Epub 2006 Feb 19. (http://www.ncbi.nlm.nih.gov/pubmed/16491085?dopt=Abstract)
Pearl PL, Taylor JL, Trzcinski S, Sokohl A. The pediatric neurotransmitter disorders. J Child Neurol. 2007 May;22(5):606-16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17690069?dopt=Abstract)
Plecko B, Paul K, Paschke E, Stoeckler-Ipsiroglu S, Struys E, Jakobs C, Hartmann H, Luecke T, di Capua M, Korenke C, Hikel C, Reutershahn E, Freilinger M, Baumeister F, Bosch F, Erwa W. 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. (http://www.ncbi.nlm.nih.gov/pubmed/17068770?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.