Indeed, multiple studies have shown that IDS variants that disrupt idursulfase expression – such as large deletions, frameshifts and recombinations – are associated with neuronopathic phenotypes in MPS II, whereas variants impairing activity but still allowing the enzyme to be expressed may result in non-neuronopathic clinical presentations [4, 19, 20], in line with our findings. This evidence concerns the gene IDS and mucopolysaccharidosis type 2.