Hunter Syndrome

Hunter syndrome (mucopolysaccharidosis type II) is an X-linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase, an enzyme essential for degrading heparan sulfate and dermatan sulfate glycosaminoglycans. Without adequate enzyme activity, these substrates accumulate within lysosomes in cells throughout the body. The severe form typically manifests between ages 2-4 years with developmental delay, coarse facial features, hepatosplenomegaly, joint stiffness, and progressive neurological decline including intellectual disability and behavioral problems. Hearing loss is nearly universal and often requires early intervention. The attenuated form has later onset (4-10 years), slower progression, normal or near-normal intellectual development, and longer lifespan. Both forms eventually cause progressive multisystem disease affecting growth, mobility, hearing, cardiac function, and cognition. Enzyme replacement therapy (idursulfase) can improve some manifestations, slow disease progression, and improve lifespan, particularly when started early.