見逃さない！SOD1–ALSの臨床的特徴

抄録

With the advent of tofersen, the landscape of clinical practice is poised to change dramatically not only for familial amyotrophic lateral sclerosis (ALS) but also for sporadic ALS. Mutations in the SOD1 gene are found in approximately 30% of familial ALS and 1.5% of sporadic ALS cases. This has raised the critical issue of how early a diagnosis can be made and treatment initiated. Therefore, it is essential to pursue the diagnostic process with the clinical characteristics of SOD1–ALS clearly in mind.

Typical features of SOD1–ALS include a younger age at onset compared with sporadic ALS, most commonly a lower–limb phenotype with asymmetric involvement, and a relatively slow disease course. Upper motor neuron signs are often absent. Some patients with SOD1–ALS may exhibit a phenotype resembling hereditary peripheral neuropathy. However, depending on the specific gene mutation, some patients develop a rapidly progressive course, and in such cases the disease may be indistinguishable from sporadic ALS. Some patients complain of numbness or sensory disturbances, and abnormalities of sensory nerves may be detected on nerve conduction studies. In addition, although rare, autonomic failure may be observed in advanced stages.

Even in advanced cases, establishing a diagnosis of SOD1–ALS is important, as it has implications for the early diagnosis and early treatment of affected family members. Needless to say, when diagnosing SOD1–ALS, adequate systems of genetic counselling should be in place.