National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Pyridoxine-dependent epilepsy


Other Names:
Pyridoxine dependency; Pyridoxine dependency with seizures; Vitamin B6-dependent seizures; Pyridoxine dependency; Pyridoxine dependency with seizures; Vitamin B6-dependent seizures; Antiquitin deficiency See More
Categories:
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). 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). Mutations in the ALDH7A1 gene cause pyridoxine-dependent epilepsy. This gene is inherited in an autosomal recessive fashion.[1]
Last updated: 7/23/2013
Those affected by pyridoxine-dependent epilepsy 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.  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.[1]
Last updated: 7/23/2013

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality
[ more ] 		0001939
Abnormality of movement
Movement disorder
Unusual movement
[ more ] 		0100022
EEG abnormality 0002353
Global developmental delay 0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment
[ more ] 		0002167
Status epilepticus
Repeated seizures without recovery between them
0002133
30%-79% of people have these symptoms
Muscular hypotonia
Low or weak muscle tone
0001252
5%-29% of people have these symptoms
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Hepatomegaly
Enlarged liver
0002240
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Ventriculomegaly 0002119
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Bilateral tonic-clonic seizure
Grand mal seizures
0002069
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
Fetal distress 0025116
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Generalized myoclonic seizure 0002123
Neonatal respiratory distress
Infantile respiratory distress
Newborn respiratory distress
Respiratory distress, neonatal
[ more ] 		0002643
Prenatal movement abnormality 0001557
Respiratory distress
Breathing difficulties
Difficulty breathing
[ more ] 		0002098
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Last updated: 7/1/2020

Mutations in the ALDH7A1 gene cause 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.[1]

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.[1]

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.[1]

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.[1]

Last updated: 7/23/2013

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
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).[1][2] Recent studies have focused on using a lysine-restricted diet in addition to pyridoxine. Preliminary results suggest that this treatment has the potential to help control seizures and improve developmental outcomes in children with pyridoxine-dependent epilepsy.[3]
Last updated: 7/23/2013

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other causes of neonatal epileptic encephalopathy such as inborn errors of metabolism (e.g. glucose transporter type I deficiency, 4-hydroxybutyric aciduria and molybdenum cofactor deficiency), single gene defects and fetal or neonatal brain injury. Pyridoxal phosphate-responsive seizures, hyperprolinemia type 2 and infantile hypophosphatasia (see these terms) should also be excluded.
Visit the Orphanet disease page for more information.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Pyridoxine-dependent epilepsy. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Pyridoxine-dependent epilepsy. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My daughter was diagnosed with pyridoxine-dependent epilepsy at birth. Her symptoms were controlled until a few years ago when she began to have muscle stiffness in the hands and legs, partial seizures, and loss of her voice. Her seizures now occur almost daily and are quite violent. Her doctors believe that her seizure activity may now be the result of psychogenic nonepileptic seizures (PNES). Is this a common occurrence in adults with pyridoxine-dependent epilepsy? See answer


  1. Pyridoxine-dependent epilepsy. Genetics Home Reference (GHR). 2013; http://ghr.nlm.nih.gov/condition=pyridoxinedependentepilepsy. Accessed 7/23/2013.
  2. Gospe SM. Pyridoxine-Dependent Seizures. GeneReviews. 2012; http://www.ncbi.nlm.nih.gov/books/NBK1486/. Accessed 7/23/2013.
  3. van Karnebeek CD et al. Lysine restricted diet for pyridoxine-dependent epilepsy: first evidence and future trials. Mol Genet Metab. 2012 Nov;107(3):335-44. .