Clinical Information

Mucopolysaccharidosis II (MPS II; Hunter syndrome) is an X-linked lysosomal disorder caused by the deficiency of iduronate sulfatase enzyme due to variants in the IDS gene. Clinical features and severity of symptoms are widely variable ranging from severe infantile onset disease to an attenuated form, which generally has a later onset with a milder clinical presentation. Symptoms may include coarse facies, short stature, enlarged liver and spleen, hoarse voice, stiff joints, cardiac disease, and profound neurologic involvement leading to developmental delays and regression. As an X-linked disorder, MPS II occurs primarily in male patients with an estimated incidence of 1 in 120,000 male births, although symptomatic carrier females have been reported. Treatment availability, including hematopoietic stem cell transplantation and enzyme replacement therapy, makes early diagnosis desirable, as early initiation of treatment has been shown to improve clinical outcomes. Newborn screening for MPS II has been implemented in some states.

A diagnostic workup in an individual with MPS II includes urine or blood glycosaminoglycans levels showing increased amounts of both dermatan and heparan sulfate (see MPSQU / Mucopolysaccharides Quantitative, Random, Urine and MPSBS / Mucopolysaccharidosis, Blood Spot). Reduced or absent activity of iduronate sulfatase can confirm a diagnosis of MPS II but may also be deficient in unaffected individuals with pseudodeficiency as well as individuals with multiple sulfatase deficiency. Enzymatic testing is not reliable to detect carriers. Molecular genetic testing of the IDS gene allows for detection of the disease-causing variant in affected patients and subsequent carrier detection in female relatives (see MPS2Z / Hunter Syndrome, Full Gene Analysis, Varies).