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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Anemia	-
Autosomal recessive inheritance	-
Decreased CSF homovanillic acid	-
Encephalopathy	-
Failure to thrive	-
Feeding difficulties in infancy	-
Hypoglycemia	-
Increased serum lactate	-
Metabolic acidosis	-
Muscular hypotonia of the trunk	-
Myoclonus	-
Premature birth	-
Progressive microcephaly	-
Seizures	-

Last updated: 10/1/2016

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.

Do you have updated information on this condition? Let us know.

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.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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.

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.

GARD Answers GARD Answers

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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