Pyridoxal 5'-phosphate-dependent epilepsy

Title

Other Names:

Pyridoxine-5'-phosphate oxidase deficiency; PNPO Deficiency; Pyridoxamine 5-prime-phosphate oxidase deficiency; Pyridoxine-5'-phosphate oxidase deficiency; PNPO Deficiency; Pyridoxamine 5-prime-phosphate oxidase deficiency; PNPO-related neonatal epileptic encephalopathy See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary Summary

Pyridoxal 5'-phosphate-dependent epilepsy is a rare genetic metabolic disorder. Babies born with this disorder are not able to make enough Vitamin B6 and this causes the baby to start having seizures soon after they are born (also called early onset or neonatal onset seizures). The normal drugs to treat seizures (anti-seizure medications or anti-convulsants) do not work for these babies, however seizures can be controlled by pyridoxal 5'-phosphate (the active form of Vitamin B6).^[1]^[2]^[3] Published studies in 2015 have shown that some babies with pyridoxal 5'-phosphate-dependent epilepsy also respond well to pyridoxene (a different form of Vitamin B6).^[2]

Pyridoxal 5'-phosphate-dependent epilepsy is caused by changes or mutations in the PNPO gene and is inherited in an autosomal recessive manner.^[1]^[2]^[3] Diagnosis is suspected by early onset of seizures which are not controlled by normal anti-seizure medications. Genetic testing is used to confirm the diagnosis. The disorder is fatal without treatment. Early treatment is important to decrease the chance of long term developmental delays. Some babies with early treatment have developed normally without any intellectual disabilities. There are less than 50 known cases of pyridoxal 5'-phosphate-dependent epilepsy as of 2015.^[1]^[2]

Last updated: 9/23/2016

Symptoms Symptoms

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
Epileptic encephalopathy		0200134
Status epilepticus	Repeated seizures without recovery between them	0002133
30%-79% of people have these symptoms
Abnormality of eye movement	Abnormal eye movement Abnormal eye movements Eye movement abnormalities Eye movement issue [ more ]	0000496
Abnormality of the amniotic fluid		0001560
Decreased CSF homovanillic acid		0003785
EEG with burst suppression		0010851
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Global brain atrophy	Generalized brain degeneration	0002283
Global developmental delay		0001263
High-pitched cry		0025430
Hypertonia		0001276
Hypoargininemia	Low blood arginine levels	0005961
Hypoglycemia	Low blood sugar	0001943
Increased serum lactate		0002151
Low APGAR score		0030917
Metabolic acidosis		0001942
Muscular hypotonia of the trunk	Low muscle tone in trunk	0008936
Myoclonus		0001336
Premature birth	Premature delivery of affected infants Preterm delivery [ more ]	0001622
Unsteady gait	Unsteady walk	0002317
5%-29% of people have these symptoms
Abnormal circulating glycine concentration		0010895
Abnormal circulating histidine concentration		0010904
Abnormal circulating threonine concentration		0010900
Abnormal circulating tyrosine concentration		0010917
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Pyridoxine-responsive sideroblastic anemia		0005522
Percent of people who have these symptoms is not available through HPO
Anemia	Low number of red blood cells or hemoglobin	0001903
Autosomal recessive inheritance		0000007
Encephalopathy		0001298
Feeding difficulties in infancy		0008872
Progressive microcephaly	Progressively abnormally small cranium Progressively abnormally small skull [ more ]	0000253
Rotary nystagmus		0001583
Seizure		0001250

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 9/1/2020

Do you have updated information on this disease? We want to hear from you.

Inheritance Inheritance

Pyridoxal 5'-phosphate-dependent epilepsy is inherited in an autosomal recessive manner.^[1]^[2]^[3] This means for a baby to have this type of epilepsy, they must have a mutation in both copies of the PNPO gene in each cell. People with pyridoxal 5'-phosphate-dependent epilepsy inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

25% chance to be affected
50% chance to be an unaffected carrier like each parent
25% chance to be unaffected and not a carrier

When a person with pyridoxal 5'-phosphate-dependent epilepsy (so has two copies of the changed gene) has children, the risk their child will be affected by this type of epilepsy is dependent on whether their partner has mutations in one or both of their PNPO genes. If the partner does not have any mutation in the PNPO gene, then each child will be an unaffected carrier of the disorder. Therefore talking to a genetic counselor before becoming pregnant is advised.

Last updated: 9/23/2016

Diagnosis Diagnosis

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.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Learn More Learn More

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 Pyridoxal 5'-phosphate-dependent epilepsy. This website is maintained by the National Library of Medicine.

In-Depth Information

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 Pyridoxal 5'-phosphate-dependent epilepsy. Click on the link to view a sample search on this topic.

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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.

Have a question? Contact a GARD Information Specialist.

References References

Guerin A, Aziz AS, Mutch C, Lewis J, Go CY, and Mercimek-Mahmutoglu S. Pyridox(am)ine-5-Phosphate Oxidase Deficiency Treatable Cause of Neonatal Epileptic Encephalopathy With Burst Suppression: Case Report and Review of the Literature. J Child Neurol. August 2015; 30(9):1218-25. https://www.ncbi.nlm.nih.gov/pubmed/25296925.
Veeravigrom M, Damrongphol P, Ittiwut R, Ittiwut C, Suphapeetiporn K, and Shotelersuk V. Pyridoxal 5'-phosphate-responsive epilepsy with novel mutations in the PNPO gene: a case report. Genet Mol Res. October 30 2015; 14(4):14310-5. https://www.ncbi.nlm.nih.gov/pubmed/26535729.
Kniffen CL. Pyridoxal 5-Prime-Phosphate Oxidase Deficiency. Online Mendelian Inheritance in Man. March 1 2016; http://www.omim.org/entry/610090.

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