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Pyridoxine-Dependent Epilepsy via the ALDH7A1 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
4091 ALDH7A1 81406 81406,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4091ALDH7A181406 81406,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Pyridoxine-dependent epilepsy is an infantile onset seizure disorder with seizures that respond to treatment with pyridoxine. Classic PDE patients present with clonic seizures or myoclonic jerks within the first minutes to months of life (Mills et al. 2010). These seizures are resistant to standard anticonvulsants, but are well controlled by pharmacological introduction of pyridoxine. Continuous treatment of pyridoxine is required to maintain seizure control. EEGs may show a burst-suppression pattern, but there is no characteristic electrophysiological sign that defines PDE (Mills et al. 2010). In addition to seizures, PDE patients often have mild to moderate intellectual disability (ID) or autistic features (Bok et al. 2012). ID persists even with early and continuous pyridoxine treatment. PDE patients have increased levels of the metabolic intermediates alpha-aminoadipic semialdehyde (AASA) and/or piperideine-6-carboxylate (P6C) in the urine or pipecolic acid (PA) in the plasma (Struys et al. 2012a; Plecko et al. 2007). Elevated AASA levels are not exclusive to PDE and are also observed in molybdenum cofactor deficiency and sulfite oxidase deficiency (Struys et al. 2012b). In the past, seizure response to pyridoxine followed by seizure recurrence upon controlled pyridoxine withdrawal was used as another diagnostic indicator of PDE (Mills et al. 2006).

Genetics

PDE is inherited in an autosomal recessive manner and is caused by mutations in the ALDH7A1 gene. Missense, nonsense, frameshift, and splice site mutations as well as large deletions in ALDH7A1 have been reported in PDE patients (Mills et al. 2010; Plecko et al. 2007). ALDH7A1 encodes the enzyme antiquitin which is required for cerebral lysine degradation. Loss of antiquitin function leads to accumulation of a metabolic intermediate which inactivates pyridoxal-5' phosphate (PLP), the biologically active vitamer of B6/pyridoxine (Plecko et al. 2007). PLP is required as a coenzyme for synthesis of many neurotransmitters and it is believed that loss of these neurotransmitters underlies the epilepsy phenotype. Supplementation of pyridoxine is able to compensate for the PLP deficiency caused by loss of antiquitin and is effective at controlling seizures.

Clinical Sensitivity - Sequencing with CNV PG-Select

ALDH7A1 variants were identified in 27 of 30 (90%) families with elevated AASA levels or a clinical diagnosis of PDE (Mills et al. 2010). In another study, ALDH7A1 variants were found in 14 of 16 (88%) families with elevated AASA and PA levels (Plecko et al. 2007).

Testing Strategy

This test provides full coverage of all coding exons of the ALDH7A1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

ALDH7A1 testing is recommended for patients with neonatal onset seizures that respond to pyridoxine treatment and who have elevated levels of AASA in urine. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ALDH7A1.

Gene

Official Gene Symbol OMIM ID
ALDH7A1 107323
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Pyridoxine-Dependent Epilepsy AR 266100

Citations

  • Bok LA, Halbertsma FJ, Houterman S, Wevers RA, Vreeswijk C, Jakobs C, Struys E, Der Hoeven JH Van, Sival DA, Willemsen MA. 2012. Long-term outcome in pyridoxine-dependent epilepsy: Long-Term Outcome in Pyridoxine-Dependent Epilepsy. Developmental Medicine & Child Neurology 54: 849–854. PubMed ID: 22804844
  • Mills PB, Footitt EJ, Mills KA, Tuschl K, Aylett S, Varadkar S, Hemingway C, Marlow N, Rennie J, Baxter P, Dulac O, Nabbout R, et al. 2010. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency). Brain 133: 2148–2159. PubMed ID: 20554659
  • Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MAAP, Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT. 2006. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nature Medicine 12: 307–309. PubMed ID: 16491085
  • Plecko B, Paul K, Paschke E, Stoeckler-Ipsiroglu S, Struys E, Jakobs C, Hartmann H, Luecke T, Capua M di, Korenke C, Hikel C, Reutershahn E, et al. 2007. Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene. Human Mutation 28: 19–26. PubMed ID: 17068770
  • Struys EA, Bok LA, Emal D, Houterman S, Willemsen MA, Jakobs C. 2012a. The measurement of urinary Δ1-piperideine-6-carboxylate, the alter ego of α-aminoadipic semialdehyde, in Antiquitin deficiency. Journal of Inherited Metabolic Disease 35: 909–916. PubMed ID: 22249334
  • Struys EA, Nota B, Bakkali A, Shahwan S Al, Salomons GS, Tabarki B. 2012b. Pyridoxine-dependent Epilepsy With Elevated Urinary -Amino Adipic Semialdehyde in Molybdenum Cofactor Deficiency. PEDIATRICS 130: e1716–e1719. PubMed ID: 23147983

Ordering/Specimens

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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