Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase, which is necessary for breaking down the glycosaminoglycans dermatan sulfate and heparan sulfate. The disorder results from mutations in the IDS gene. Without sufficient enzyme activity, GAGs accumulate inside lysosomes, leading to progressive cellular dysfunction and damage across multiple organ systems, particularly the skeletal, cardiovascular, respiratory, and nervous systems. MPS II presents as a spectrum ranging from severe neurologic involvement to milder attenuated disease.

Symptoms usually appear in early childhood and worsen over time. Common features include: • Coarse facial features • Short stature and skeletal abnormalities • Joint stiffness and limited mobility • Enlarged liver and spleen Additional symptoms may include: • Hearing loss and recurrent ear infections • Chronic respiratory disease • Heart valve abnormalities • Behavioral problems and hyperactivity • Progressive cognitive decline in severe forms Unlike MPS I, corneal clouding is usually absent, which is an important distinguishing feature. Life expectancy depends on disease severity, with severe forms often leading to death in adolescence or early adulthood.

MPS II is caused by mutations in the IDS gene.

Diagnosis includes: • Elevated urinary GAG levels • Enzyme assays demonstrating deficient iduronate-2-sulfatase • Genetic testing for IDS mutations Prenatal testing is possible in families with known mutations.

Treatment focuses on slowing progression and managing symptoms. Options include: • Enzyme replacement therapy (ERT) • Supportive care addressing cardiac, respiratory, and orthopedic complications • Physical, occupational, and speech therapy ERT improves somatic symptoms but has limited effect on neurologic disease.