GABA Metabolism Deficiency


Test Details
TEST CODE NGS310
TEST METHODOLOGY NGS
TAT (TURNAROUND TIME) 2 - 4 weeks
GENES 15
CPT CODE 81479
PRICE $1795
RECOMMENDED MNG KITS
  • SINGLE Blood Genetic Testing
  • Buccal Swab Genetic Testing

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Clinical Information
Clinical Significance

Defects have been reported in 4 steps of the gamma amino butyric acid (GABA) metabolism causing inherited disorders as: glutamate decarboxylase (GAD) deficiency, GABA-transaminase deficiency, succinic semialdehyde dehydrogenase (SSADH) deficiency, and homocarnosinase deficiency. SSADH deficiency is the most common of the inherited disorders of neurotransmitters. GABA-transaminase deficiency and homocarnosinosis appear to be very rare.

SSADH deficiency is an autosomal recessive inherited condition characterized by infantile-onset of hypotonia, developmental delay, cognitive impairment, expressive language deficit, and mild ataxia. Epilepsy is present in about half of affected individuals and is more common in adults. Hyperkinetic behavior, aggression, self-injurious behaviors, hallucinations, and sleep disturbances have been reported in nearly half of all affected individuals, more commonly in those who are older.

GAD deficiency is inherited in an autosomal recessive manner and is caused by pathogenic variants in the GAD1 gene. GAD1 catalyzes the conversion of glutamic acid to GABA. GAD deficiency is a non-progressive disorder of movement and/or posture. Affected individuals manifest symmetrical, non-progressive spasticity, developmental delay, hypertonia, and sometimes intellectual disability and epilepsy can be part of the clinical picture.

GABA-transaminase deficiency is a very rare autosomal recessive condition caused by pathogenic variants in the ABAT gene. The phenotype includes severe intellectual disability, hypotonia, hyperreflexia, lethargy, refractory seizures, high-pitched cry, and EEG abnormalities.

Relevant Diseases
  • GABA Metabolism Disorders

Specimen Information
Acceptable Sample Types
  • Muscle
  • Cultured Fibroblasts
  • Whole Blood - EDTA
  • Extracted DNA - Leukocytes
  • Buccal Cells
Sample Preparation: (1) Blood specimens: Draw blood in an EDTA tube. Preferred volume: 4 milliliters (adults and pediatrics), Minimum volume: 2 milliliters; (2) DNA extracted from leukocytes, muscle, or fibroblasts: Preferred quantity: 4 micrograms, Minimum quantity: 3 micrograms (Genomic DNA should be eluted in sterile Dnase/Rnase free water or TE. The A260:A280 ratio should be 1.8-2.0.); (3) 2 T-25 flasks of fibroblasts; (4) 50-75 milligrams muscle snap frozen in liquid nitrogen and maintained at -80┬░Celsius or below. (5) Skin biopsy (Fibroblasts will be cultured from skin specimen for genetic testing): Skin biopsy may be taken from the inner forearm with a sterile skin punch (2-5 millimeters) or at incision site of muscle biopsy. Site is sterilized with alcohol swabs only (other reagents will inhibit cell isolation/growth). Biopsy site may be anaesthetized with 2% lidocaine with epinephrine. Depth of punch is 2mm. Transfer skin biopsy into 15 milliliter conical tube filled with sterile culture media. (6) Buccal cells.
Shipping Condition: MNG SmartKits are available for free shipping of specimens. Please see our website for details. If you are not using a MNG SmartKit: (1) Blood specimens should be shipped in a secure container at room temperature. (2) Extracted DNA should be shipped priority overnight at ambient temperature. (3) T-25 flasks containing fibroblasts should be shipped in an insulated container at room temperature. Flasks should be completely filled with media and cells should be ~90% confluent. Fibroblast samples must be certified free from Mycoplasma. MNG is able to perform this service for a small charge (See TC05). (4) Muscle samples should be shipped frozen in an insulated container with 5-7 lbs dry ice. (5) Buccal cells should be shipped in a secure container at room temperature. (6) Skin Biopsy: Conical containing the skin specimen should be shipped in a secure container with cold pack (DO NOT FREEZE). All samples should be shipped overnight at the proper temperature for receipt by our lab Monday thru Saturday (No Sunday or holiday deliveries accepted).

Genes Assessed
ABAT
ALDH5A1
CACNA1A
CACNA1B
GABRB3
GABRD
GABRG2
GAD1
GLUL
GNAQ
GPHN
PHGDH
SLC1A3
SLC6A1
SNCA

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