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Pyridoxine 5'-Phosphate Oxidase Deficiency via the PNPO Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
PNPO 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4219PNPO81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Pyridoxine 5'-phosphate oxidase deficiency (PNPO deficiency) is an inborn error of metabolism that results in neonatal epileptic encephalopathy. Seizure onset in PNPO deficiency occurs within the first hours to weeks of life. Seizure types include clonic, myoclonic, tonic, and/or generalized tonic-clonic seizures that are resistant to treatment with anti-epileptic drugs (Mills et al. 2014). Seizures are responsive to treatment with pyridoxal-5'-phosphate (PLP) or, in some cases, pyridoxine. Common EEG findings include burst-suppression pattern and hypsarrhythmia (Mills et al. 2014). Other variable features seen in infants with PNPO deficiency include hypotonia, acidosis, speech delay, and liver function abnormalities.

Indications of possible PNPO deficiency include: 1. elevated threonine and glycine levels in the CSF and plasma and 2. rapid response to treatment with either PLP or pyridoxine (Mills 2005). In contrast to patients with antiquitin deficiency, who also respond to pyridoxine treatment, patients with PNPO deficiency do not have elevated AASA or PA concentrations (Mills 2005; Plecko et al. 2014).


PNPO deficiency is inherited in an autosomal recessive manner and is caused by variants in the PNPO gene. Pathogenic missense, splice site, nonsense and frameshift variants have been reported in the PNPO gene (Plecko et al. 2014).

PNPO encodes the enzyme pyridoxine 5'-phosphatase oxidase (PNPO). Vitamin B6 enters the blood stream as pyridoxine, pyridoxamine, or pyridoxal. PNPO is required to convert pyridoxine, and pyridoxamine into the active vitamer, pyridoxal-5'-phosphate (PLP). PLP is a co-enzyme required for a range of cellular enzymatic reactions. Treatment with PLP bypasses the need for the PNPO enzyme in patients with PNPO deficiency. Interestingly, a number of PNPO cases have been reported in which the patient responds favorably to treatment with pyridoxine (Pearl et al. 2012). This suggests that in some cases PNPO enzyme activity is not completely lost and that PNPO can still convert pyridoxine to PLP in the presence of excess substrate.

Clinical Sensitivity - Sequencing with CNV PG-Select

PNPO was sequenced in 31 individuals with pyridoxine-responsive seizures who tested negative for ALDH7A1 deficiency; pathogenic variants were identified in ~30% (9 of 31) individuals (Plecko et al. 2014). In another study pathogenic PNPO variants were found in ~16% (13 of 82) individuals with PLP responsive seizures (Mills et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the PNPO gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

PNPO sequencing is recommended for patients with onset of seizures within the first week of life that are refractory to anti-epileptic drugs, but responsive to supplementation with PLP or pyridoxine. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PNPO.


Official Gene Symbol OMIM ID
PNPO 603287
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Pyridoxal 5'-Phosphate-Dependent Epilepsy AR 610090


  • Mills PB, Camuzeaux SSM, Footitt EJ, Mills KA, Gissen P, Fisher L, Das KB, Varadkar SM, Zuberi S, McWilliam R, Stodberg T, Plecko B, Baumgartner MR, Maier O, Calvert S, Riney K, Wolf NI, Livingston JH, Bala P, Morel CF, Feillet F, Raimondi F, Del Giudice E, Chong WK, Pitt M, Clayton PT. 2014. Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome. Brain 137: 13501360. PubMed ID: 24645144
  • Mills PB. 2005. Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5-phosphate oxidase. Human Molecular Genetics 14: 10771086. PubMed ID: 15772097
  • Pearl PL, Hyland K, Chiles J, McGavin CL, Yu Y, Taylor D. 2012. Partial Pyridoxine Responsiveness in PNPO Deficiency. In: Zschocke J, Gibson KM, Brown G, Morava E, and Peters V, editors. JIMD Reports - Case and Research Reports, 2012/6, Berlin, Heidelberg: Springer Berlin Heidelberg, p 139142. PubMed ID: 23430561
  • Plecko B, Paul K, Mills P, Clayton P, Paschke E, Maier O, Hasselmann O, Schmiedel G, Kanz S, Connolly M, Wolf N, Struys E, Stockler S, Abela L, Hofer D. 2014. Pyridoxine responsiveness in novel mutations of the PNPO gene. Neurology 82: 14251433. PubMed ID: 24658933


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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View Ordering Instructions

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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