Pyridoxal 5'-phosphate-dependent epilepsy is a condition that involves seizures beginning soon after birth or, in some cases, before birth. The seizures typically involve irregular involuntary muscle contractions (myoclonus), abnormal eye movements, and convulsions. Most babies with this condition are born prematurely and may have a temporary, potentially toxic, increase in lactic acid in the blood (lactic acidosis). Additionally, some infants have a slow heart rate and a lack of oxygen during delivery (fetal distress).
Anticonvulsant drugs, which are usually given to control seizures, are ineffective in people with pyridoxal 5'-phosphate-dependent epilepsy. Instead, individuals with this type of epilepsy are medically treated with large daily doses of pyridoxal 5'-phosphate (a form of vitamin B6). If left untreated, people with this condition can develop severe brain dysfunction (encephalopathy), which can lead to death. Even though seizures can be controlled with pyridoxal 5'-phosphate, neurological problems such as developmental delay and learning disorders may still occur.
Pyridoxal 5'-phosphate-dependent epilepsy is a rare condition; approximately 14 cases have been described in the scientific literature.
Mutations in the PNPO gene cause pyridoxal 5'-phosphate-dependent epilepsy. The PNPO gene provides instructions for producing an enzyme called pyridoxine 5'-phosphate oxidase. This enzyme is involved in the conversion (metabolism) of vitamin B6 derived from food (in the form of pyridoxine and pyridoxamine) to the active form of vitamin B6 called pyridoxal 5'-phosphate (PLP). PLP is necessary for many processes in the body including protein metabolism and the production of chemicals that transmit signals in the brain (neurotransmitters).
PNPO gene mutations result in a pyridoxine 5'-phosphate oxidase enzyme that is unable to metabolize pyridoxine and pyridoxamine, leading to a deficiency of PLP. A shortage of PLP can disrupt the function of many other proteins and enzymes that need PLP in order to be effective. It is not clear how the lack of PLP affects the brain and leads to the seizures that are characteristic of pyridoxal 5'-phosphate-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.
Other Names for This Condition
- PNPO deficiency
- PNPO-related neonatal epileptic encephalopathy
- Pyridoxamine 5-prime-phosphate oxidase deficiency
- Pyridoxine-5'-phosphate oxidase deficiency
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Bagci S, Zschocke J, Hoffmann GF, Bast T, Klepper J, Muller A, Heep A, Bartmann P, Franz AR. Pyridoxal phosphate-dependent neonatal epileptic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2008 Mar;93(2):F151-2. doi: 10.1136/adc.2006.115162. Citation on PubMed
- Hoffmann GF, Schmitt B, Windfuhr M, Wagner N, Strehl H, Bagci S, Franz AR, Mills PB, Clayton PT, Baumgartner MR, Steinmann B, Bast T, Wolf NI, Zschocke J. Pyridoxal 5'-phosphate may be curative in early-onset epileptic encephalopathy. J Inherit Metab Dis. 2007 Feb;30(1):96-9. doi: 10.1007/s10545-006-0508-4. Epub 2006 Dec 23. Citation on PubMed
- Khayat M, Korman SH, Frankel P, Weintraub Z, Hershckowitz S, Sheffer VF, Elisha MB, Wevers RA, Falik-Zaccai TC. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism. Mol Genet Metab. 2008 Aug;94(4):431-434. doi: 10.1016/j.ymgme.2008.04.008. Epub 2008 May 15. Citation on PubMed
- Mills PB, Surtees RA, Champion MP, Beesley CE, Dalton N, Scambler PJ, Heales SJ, Briddon A, Scheimberg I, Hoffmann GF, Zschocke J, Clayton PT. Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. Hum Mol Genet. 2005 Apr 15;14(8):1077-86. doi: 10.1093/hmg/ddi120. Epub 2005 Mar 16. Citation on PubMed
- Plecko B, Mills P. PNPO Deficiency. 2022 Jun 23. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK581452/ Citation on PubMed