ADA and Global developmental delay: Nevertheless, expression of ectopic ADA in the brain may be relevant, because many patients experience neurological symptoms, including hearing loss, cognitive delay, and hyperactivity disorders associated with several MRI abnormalities, white matter alterations, and motor dysfunctions that are not corrected fully with ERT, HSCT, or HSC GT.27, 28, 29 Although rAAV8 resulted in limited brain marking, pre-clinical and clinical studies using rAAV9 have demonstrated transfer across the BBB,30,31 and perhaps additional studies with different serotypes are warranted.