Skin fibroblasts cultured from patients affected with the Hunter syndrome are deficient in the activity of a protein, named the "Hunter corrective factor," that is required for degradation of dermatan and heparan sulfates. We now show that this factor, purified from human urine, removes about 2% of the sulfate residues from [3aS]mucopolysaccharide accumulated within Hunter fibroblasts; these groups are derived from "oversulfated" regions of the polymer. Acetone-powder extracts of fibroblasts derived from patients with the Hunter syndrome are deficient in this sulfatase, in contrast to similar extracts from fibroblasts of individuals of other genotype. Hunter corrective factor coupled to a-L-iduronidase (or alternatively, mixed extracts from Hurler and Hunter fibroblasts) release iduronic acid from 4-0-a-L-sulfoiduronosyl-Dsulfoanhydromannose. We conclude that the Hunter corrective factor is a sulfatase for sulfated iduronic acid residues.The Hunter syndrome is a genetic disorder associated with failure to degrade dermatan sulfate and heparan sulfate; lysosomal storage of these polymers leads to numerous clinical problems, including skeletal abnormalities, limitation of joint motion, hepatosplenomegaly, deafness, and cardiovascular disease (1, 2). Of the known mucopolysaccharidoses, the Hunter syndrome is the only one transmitted as an X-linked recessive trait.Fibroblasts cultured from the skin of Hunter patients do not adequately degrade sulfated mucopolysaccharide because of a deficiency of a specific protein that is present in cell secretions, cells, and urine of individuals who do not have the Hunter syndrome (3-5). Because this protein, when added exogenously to Hunter cells, accelerates the degradation of sulfated mucopolysaccharide, it has been named the "Hunter corrective factor," and abbreviated simply as "Hunter factor." Purified Hunter factor has no effect on the mucopolysaccharide metabolism of cells derived from normal individuals or from patients with mucopolysaccharide storage disorders other than the Hunter syndrome (5).Several analogous corrective factors have recently been identified as the "missing enzyme" in the corresponding disorder. Thus, the Hurler corrective factor has been identified as the enzyme a-iiduronidase, and the Hurler and Scheie syndromes as a-riduronidase deficiency diseases (6, 7); the Sanfilippo A corrective factor has been identified as heparan sulfate sulfatase (probably an N-sulfatase) (8), and the Sanfilippo B factor as N-acetyl-a-glucosaminidase (9,10). In a mucopolysaccharidosis due to #3-glucuronidase (EC 3.2.1.31) deficiency, jB-glucuronidase serves as corrective factor (11).We have now identified the Hunter corrective factor as a sulfatase for sulfated iduronic
