Quantitative and qualitative analysis of urinary GAGs is helpful as a preliminary MPS screening test; however, demonstration of I2S deficiency and normal level of at least one sulphatase to exclude SUMF1 deficiency (sulfatase modifying factor 1) in dry blood spot, leukocytes, fibroblasts, or plasma is necessary for MPS II diagnosis confirmation in a male proband. This evidence concerns the gene SUMF1 and mucopolysaccharidosis type 2.