SMN1 and amyotrophic lateral sclerosis: However, one form or the other of alteration of RNA expression may have different weight in different MNDs and, most importantly, RNA dysmetabolisms may be a primary event (for instance in SMA or in TDP43- and FUS/TLS-linked ALS) or dysregulation of components of the genetic machinery (the HATs/HDACs system, transcription factors, the splicing complex) may be secondary to oxidative stress or energy failure.