Amyotrophic Lateral Sclerosis (ALS) Testing Program
Program Overview
In partnership with Ionis, this program provides genetic testing for amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by motor neuron impairment in the cortex, brain stem, and spinal cord. ALS testing is available for patients with a clinical diagnosis or family history of ALS. This program is currently being offered to residents of the U.S. and Canada who meet testing eligibility criteria. The test must be ordered by a qualified healthcare provider.
Clinical Features 
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron impairment in the cortex, brain stem, and spinal cord (Hardiman et al. 2017. PubMed ID: 28980624). The dysfunction and loss of neurons result in rapidly progressive muscle weakness, atrophy and ultimately paralysis of limb, bulbar and respiratory muscles (Brown and Al-Chalabi. 2017. PubMed ID: 28700839). About 50% of patients also develop cognitive and behavioral impairment and another 13% develop frontotemporal dementia (van Es et al. 2017. PubMed ID: 28552366). The mean age of symptom onset is 55 years of age for familial cases and 65 years of age for sporadic cases. The annual incidence of ALS is 2-3 per 100,000 (van Es et al. 2017. PubMed ID: 28552366; Brown and Al-Chalabi. 2017. PubMed ID: 28700839; Siddique et al. 2023. PubMed ID: 20301623).
ALS has a heterogeneous clinical presentation with variable disease progression and age-related penetrance. Classic ALS presentation occurs in ~70% of all cases. About two-thirds of classic cases present with spinal neurodegeneration primarily affecting lower leg and upper arm motor neurons and one-third of classic cases present with bulbar involvement resulting in dysartheria and/or dysphagia. Of all ALS cases, 5%-15% present with bulbar or spinal neurodegeneration and dementia; 5% present with bulbar only features without spreading to other regions; and 10% present with only lower motor neuron involvement (van Es et al. 2017. PubMed ID: 28552366; Siddique et al. 2023. PubMed ID: 20301623; Brown and Al-Chalabi. 2017. PubMed ID: 28700839).
Testing Strategy
Testing is performed concurrently. Both the C9orf72 and ATXN2 repeat expansion tests each utilize four unique gene specific assays: (1) a repeat primed PCR assay with the locus specific primer 5’ (upstream) of the repeat region (2) a repeat primed PCR assay with the locus specific primer 3’ (downstream) of the repeat region and two unique fluorescent fragment length assays. C9orf72 and ATXN2 are not included in the sequencing panel. Results for the C9orf72, ATXN2, and sequencing panel tests will be reported separately.
The sequencing panel typically provides 99.0% coverage of all coding exons of the genes listed plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.
Criteria For Test
Candidates for this test are patients in the U.S. and Canada with a clinical or suspected clinical diagnosis of ALS (with or without a family history), or who are pre-symptomatic WITH a family history of ALS. No unaffected patient under 18 are offered pre-symptomatic testing. All symptomatic patients under 18 must have clinical features documented on the order. An exception would be considered if there is a known, familial, adolescent or pediatric form of rapidly progressive ALS.
Ordering
- Determine if the individual meets eligibility criteria and discuss the test. Pre-test genetic counseling with a third party service (provided by Genome Medical) is available to patients through this sponsored testing program.
- Order the test using the U.S. test requisition form or the Canadian test requisition form.
- Collect a blood, saliva, or buccal specimen in the collection tube. For information on ordering specimen kits, see Specimen Collection and Shipping section.
- The genetic test will be processed at PreventionGenetics and the results will be sent to the ordering healthcare provider about 18 days after the lab receives the specimens and all appropriately completed paperwork. The ordering healthcare provider will discuss the results with the patient and/or caregiver. Post-test genetic counseling appointment with a third party service (provided by Genome Medical) is available to patients through this sponsored testing program.
Specimen Collection and Shipping
Specimen Collection
WHOLE BLOOD
Collect 3 ml - 5 ml of whole blood in EDTA (purple top tube) or ACD (yellow top tube).
SALIVA
OrageneTM or GeneFiXTM Saliva Collection kit used according to manufacturer instructions.
OCD-100 BUCCAL SWAB
OCD-100 Buccal Swab used according to manufacturer instructions.
Shipping and Handling Instructions
WHOLE BLOOD
DO NOT FREEZE. During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube. In cold weather include an unfrozen ice pack in the shipping container as insulation. At room temperature, blood specimens are stable for up to 48 hours. If refrigerated, blood specimens are stable for up to one week.
SALIVA AND BUCCAL
Specimens may be shipped at room temperature.
Specimen collection kits: Blood, saliva, or buccal specimen collection kits, which contain the TRF and the shipping label, may be requested through the kit order form or via the online order form.