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Test Code ALDH7A1 KN ALDH7A1 Known Mutation

Clinical System Name

ALDH7A1 Known Mutation Request

Synonyms

Antiquitin

Vitamin 6 dependent seizures

Description

This test involves targeted analysis for variants previously identified through clinical testing of a family member or  research testing of the individual.  It can be used for carrier testing for at-risk relatives and prenatal testing for confirmed carriers. Variants must be known. For full gene sequencing please see ALDH7A1 Sequencing.

 

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 symptomatic or asymptomatic individuals to establish carrier status of ALDH7A1 gene variants previously identified in family member(s)

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 Counselors: LabGC@seattlechildrens.org

Reference Range

Interpretive report will be provided

Methodology

Method: PCR + Sequencing

 

Limitations: This test is for targeted known variant analysis only.  Variants must be known.

CPT Codes

81403x1 (updated 4/28/16 by jconta)

Special Instructions

Please provide copies of proband reports when requesting known variant analysis for cases NOT performed by Seattle Children's Lab.

 

Links to:  Pyridoxine-Dependent Seizures GeneReviewPyridoxine-Dependent Seizures Registry

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.