To estimate the number of individuals carrying ALS risk variants in the United States and to project the clinical engagement required to support their longitudinal care needs.

 We developed a population model to estimate symptomatic and asymptomatic gene-positive ALS carriers across U.S. states over 10 years. ALS prevalence and incidence were derived from race-adjusted rates in the Atlanta metropolitan study and observed case counts from the National ALS Registry. Gene-positive cases were based on published frequencies for SOD1, C9orf72, FUS, and TARDBP mutations. At-risk relatives (4.25 carriers per proband) were modeled assuming autosomal-dominant inheritance, broad uptake of cascade testing, and one annual surveillance visit per asymptomatic carrier.

In year 1, the model estimated 2,704 symptomatic gene-positive ALS carriers and 10,944 asymptomatic carriers nationwide. Most states required fewer than 50 additional clinic visits annually, with 12 states in the 50–99 range. By year 10, projections rose to 7,474 symptomatic and 26,111 asymptomatic carriers. Clinical needs increased markedly: six states remained below 50 visits annually, 22 states were in the 50–99 range, 18 states in the 100–199 range, and three states exceeded 200 visits annually.

Gene-targeted testing is expected to substantially increase ALS clinic visits for asymptomatic gene carriers. While current infrastructure may accommodate the initial rise, most states will require significant expansion within a decade. ALS clinics will need to proactively plan for the seamless integration of longitudinal care for gene-positive individuals.