This has been observed in other neurodegenerative disorders, including sporadic and familial (C9orf72) ALS/ALS-FTD (frontotemporal dementia).50-53 It has been postulated that the faster progression observed in late-onset ALS cases might reflect the reduced neuronal reserve at baseline in older patients.51 This hypothesis may also apply to RFC1 disease. The gene discussed is RFC1; the disease is amyotrophic lateral sclerosis.