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Pyridoxine-Dependent Seizures Sequencing Analysis

The patients with pyridoxine-dependent seizures (PDS) classically present with neonatal seizures, unresponsive to conventional anticonvulsant therapy but which can be controlled with pyridoxine monotherapy. Less commonly, later-onset cases present through the second to third year of life. In PDS, seizures are typically prolonged but can also include self-limiting partial, generalized, atonic, or myoclonic seizures or infantile spasms. Although most PDS patients show a rapid response to pyridoxine treatment, some show a transient response to common anticonvulsants or a poor initial response to pyridoxine.

PDS, a rare autosomal recessive disease, is caused by a deficiency of the enzyme alpha-aminoadipic semialdehyde dehydrogenase, encoded by the ALDH7A1 gene. Mutations in the ALDH7A1 gene and subsequent enzyme deficiency lead to an accumulation of alpha-aminoadipic semialdehyde (AASA) and a deficiency of the active form of vitamin B6, which is needed as a cofactor for many reactions in the central nervous system including metabolism of neurotransmitters such as dopamine, glutamate, GABA and serotonin.

Mutations in the ALDH7A1 gene account for ~95% of patients with PDS who have documented elevation of AASA. All individuals studied in families with the classic neonatal presentation have at least one mutation in the ALDH7A1 gene. The detection rate for individuals with atypical presentation of pyridoxine dependent seizures is not known.

Test Name: Pyridoxine-Dependent Seizures Sequencing Analysis
Test Code:
ALDH7A1 SEQ
Test Description:
DNA sequence analysis of all 18 exons and flanking regions of the ALDH7A1 gene.
Synonyms:
antiquitin; alpha-amino adipic acid semialdehyde dehydrogenase
Indication:
This test is indicated for individuals with:
-Documented elevation of alpha-amino adipic acid semialdehyde(AASA)
- Suspected pyridoxine-dependent seizures
Related Tests: Pyridoxine-Dependent Seizures Known Mutation Analysis  
This test is used for carrier testing at-risk relatives and prenatal testing for confirmed carriers. Mutations must be known.

Clinical Links: Pyridoxine-Dependent Seizures GeneReview
Pyridoxine-Dependent Seizures Registry
Availability:
Mon - Fri
Turnaround Time:
2-3 weeks
Methodology:
Polymerase Chain Reaction (PCR) followed by Sequencing
Reference Range:
Interpretive report will be provided
Requisition:
Consent Form:
Sample Requirements: Type
Whole blood: 1-3 ml in EDTA (purple top) or ACD (yellow top)
DNA: 5-10 ug extracted DNA

Processing
Do not spin. Keep at room temperature.

Shipping
Room temperature via overnight shipping. Blood samples must be processed within 3 days of collection.
Samples Received:
Mon – Fri 8:00 am – 5:00 pm PST
Special Considerations:
Cost:
Please e-mail Lab Client Services (labclientservices@seattlechildrens.org) or call at 206-987-2617 with any billing questions
CPT Code:
Please e-mail Lab Client Services (labclientservices@seattlechildrens.org) or call at 206-987-2617 with any billing questions