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Test Code LAB1811 ALDH7A1 Sequencing

Clinical System Name

Pyroxidine Dependent Seizures (ALDH7A1) Sequencing

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.

 

ALDH7A1 full gene sequencing is appropriate for individuals with:

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

 

Also available: Targeted Gene Variant Sequencing (LAB1915) - For targeted analysis of variants previously identified through clinical testing of a family member or research testing of the individual.  Please review requirements and restrictions for testing.

Sample Requirements

Note: For patients who have had a whole blood transfusion, wait 10 days post transfusion to draw for genetic testing. No wait time is necessary for blood or saliva collection if the patient received leuko-reduced red cells or plasma.

 

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 from EDTA blood

Minimum:　10µg

Note:　Isolation of nucleic acids for clinical testing must be performed in a CLIA-certified

laboratory or a laboratory meeting equivalent requirements as determined by the CAP

and/or the CMS.　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

 

Specimen: Saliva collected using Oragene Dx OGD-575/675 collection kit.

Container: Oragene Dx OGD-575/675 collection kit

IMPORTANT NOTE: Manufacturer instructions must be followed. The Oragene Dx OGD575/675 kit is not for children under 6 months. Contact Lab Client Services for more information or to obtain a kit 206-987-2617, labclientservices@seattlechildrens.org

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
Saliva, ORAgene Dx OGD-575/675 Room Temp 2 weeks

 

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

CPT Codes

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

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.

Reference Range

Interpretive report will be provided

Requisition

Molecular Genetics

Special Instructions

Links to: Pyridoxine-Dependent Seizures GeneReview, Pyridoxine-Dependent Seizures Registry

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.