UBA5 and Global developmental delay: 1-12 The cause of the variance in clinical severity and symptoms observed in affected individuals remains to be demonstrated; however, it is hypothesized to result from differential residual UBA5 activity.5,8,9,11,12 Colin et al. 5 noted that seizures resistant to anti-seizure medication are often associated with at least one null variant, resulting in significantly reduced UBA5 activity, while developmental delay and impaired motor function, but not seizures, are observed in individuals with two missense variants that cause milder UBA5 activity loss.