Rare Oncology News

Disease Profile

Pyridoxal 5′-phosphate-dependent epilepsy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

G40.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Pyridoxine-5'-phosphate oxidase deficiency; PNPO Deficiency; Pyridoxamine 5-prime-phosphate oxidase deficiency;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

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]

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.

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

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.

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

  • MedlinePlus Genetics 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.

References

  1. 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.
  2. 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.
  3. Kniffen CL. Pyridoxal 5-Prime-Phosphate Oxidase Deficiency. Online Mendelian Inheritance in Man. March 1 2016; https://www.omim.org/entry/610090.

Rare Oncology News