Sign in →

Test Code ALDH7A1 SEQ ALDH7A1 Sequencing

Clinical System Name

ALDH7A1 Sequencing Analysis Request

Synonyms

Antiqutin

Vitamin B6 dependent seizures

Description

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.

 

 Testing is appropriate for individuals with:

  • Documented elevation of alpha-aminoadipic semialdehyde (α-AASA)
  • Suspected pyridoxine-dependent seizures 

Sample Requirements

Specimen: Whole blood, cord blood

Container(s): Lavender/EDTA, Yellow/ACD A or B

Preferred Vol: 3 mL

Minimum Vol: 1 mL

 

Note: Heparin samples (Green tops) are unacceptable.

 

Specimen: Extracted DNA

Minimum: 10µg

Note: DNA concentration minimum 50 µg/mL; 260/280 ratio 1.70-2.00

  

Specimen: Cultured cells

Acceptable:  Fibroblasts

Container(s): T-25 flasks

Preferred Vol: 2 flasks

Processing Instructions

Reject due to: Heparin

Spin: No

Aliquot: No

Temp: Refrigerate

Storage location: Molecular Genetics box in CPA refrigerator #2

 

Off-site collection: Refrigerate blood samples until ready to ship.  Transport all sample types at room temperature via overnight shipping.

Stability

Specimen Type Temperature Time
Cultured cells Room temp 3 days
Whole blood, extracted DNA Room temp 3-5 days
Whole blood, extracted DNA Refrigerated 7 days
Extracted DNA Frozen ok

 

Note: Whole blood samples > 7days may be submitted to be assessed by our lab for acceptability for testing.

Availability

STAT Performed TAT
Contact lab Monday - Friday 2-3 weeks

 

Performing Laboratory

Seattle Children's Laboratory

Department

Department:  Molecular Genetics Laboratory

Phone: 206-987-3872

 

Lab Client Services: 206-987-2617

 

Lab Genetic Counselor: LabGC@seattlechildrens.org

Reference Range

Interpretive report will be provided

Methodology

Method: Bi-directional sequencing of all 18 exons and flanking regions of the ALDH7A1 gene.

 

Limitations: Variants in the promoter region, large deletions, large duplications, or rare recombinant mutations may not be detected by this method.

CPT Codes

81406x1 (updated 4/28/16 by jconta)

Requisition

Molecular Genetics

Clinical Utility

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. Pathogenic variants in the ALDH7A1 gene and subsequent enzyme deficiency lead to an accumulation of alpha-aminoadipic semialdehyde (α-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.

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