Ataxia/Episodic Ataxia Disorders + mtDNA + SCA & FRDA Repeat Expansion Analysis
|TEST METHODOLOGY||NGS; Repeat Primed-PCR|
|TAT (TURNAROUND TIME)||2 - 4 weeks|
|CPT CODE||81460, 81465, 81404 x1, 81405 x2, 81406 x2, 81407 x1, 81408 x1, 81479, 81401 x8|
|RECOMMENDED MNG KITS||
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait, and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. Inherited (genetic) forms of ataxia must be distinguished from the many acquired (non-genetic) causes of ataxia.
The genetic forms of ataxia are diagnosed by family history, physical examination, neuroimaging, and molecular genetic testing. The hereditary ataxias can be inherited in an autosomal dominant (AD), autosomal recessive (AR), X-linked, or mitochondrial manner, and multiple genes are involved. Early-onset ataxias, under 20 years of age, tend to be of autosomal recessive inheritance (e.g. Friedreich’s ataxia) whereas the spinocerebellar ataxias (SCAs) are autosomal dominant and tend to present mostly after 20 years of age; although both recessive and dominant can occur at any age. Prevalence of the autosomal dominant cerebellar ataxias (ADCAs) is estimated to be approximately 1-5:100,000 in the population. Autosomal recessive types of hereditary ataxia account for approximately 3:100,000. The prevalence of genetic childhood ataxia varies from 0.1 to 10 cases per 100,000 people. Ataxias due to mitochondrial disease may be an under-diagnosed cause of ‘inherited’ ataxia, but the pattern of inheritance may be complex, including maternal transmission, AD and AR inheritance.
Clinical manifestations of hereditary ataxia in general are poor coordination of movement and a wide-based, uncoordinated, unsteady gait. Poor coordination of the limbs and of speech (dysarthria) are often present. Hereditary ataxia may result from one or any combination of: dysfunction of the cerebellum and its associated systems, lesions in the spinal cord, and/or peripheral sensory loss. The diagnosis of hereditary ataxia is based upon detection and neurologic examination of typical clinical signs and symptoms, a positive family history, and molecular analysis. Hereditary ataxias can be subdivided first by mode of inheritance, and secondarily by the gene in which the pathogenic variants occur.
|Acceptable Sample Types||
|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).|