iduronate2sulfatase

Iduronate-2-sulfatase (I2S) is a lysosomal hydrolase encoded by the IDS gene. It catalyzes the removal of the 2-O-sulfate group from iduronic acid residues in the glycosaminoglycans dermatan sulfate and heparan sulfate, a key step in their degradation within lysosomes. The enzyme is trafficked to lysosomes via the mannose-6-phosphate pathway.

Deficiency of iduronate-2-sulfatase causes mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome. It is inherited in an X-linked recessive manner and almost exclusively affects males; female carriers are usually asymptomatic or mildly affected.

Clinical presentation is age-dependent and multisystemic. Attenuated forms present with somatic features such as coarse facial features, hepatosplenomegaly, airway obstruction, ear and eye problems, skeletal abnormalities, joint contractures, and valvular heart disease. Severe forms include progressive neurocognitive deterioration and central nervous system involvement.

Diagnosis relies on reduced IDS enzymatic activity in leukocytes or fibroblasts and confirmation by IDS gene sequencing; elevated urinary dermatan sulfate and heparan sulfate support the diagnosis. Treatment includes enzyme replacement therapy with idursulfase (Elaprase), which can improve somatic symptoms and quality of life, and, in selected cases, hematopoietic stem cell transplantation. Supportive care is multidisciplinary.

Research continues into alternative therapies and newborn screening in some regions.