Diagnosis and therapy options in mucopolysaccharidosis II (Hunter syndrome)

Introduction: Hunter syndrome (Mucopolysaccharidosis II, MPS II) is a lysosomal storage disease inherited as an X-linked trait. The disease is progressive, affects multiple systems and is clinically heterogeneous. Patients with the so-called 'attenuated' form have somatic manifestations affecting bone, joints, respiratory, cardiac, auditory and other systems. Patients with the 'severe form' have, in addition to the somatic manifestations, neurocognitive decline.Areas covered: Diagnosis is reached with biochemical tests (urinary glycosaminoglycans [GAGs] and enzyme assay), usually complemented with genetic analysis. Mutation identification could play a role in phenotype prediction and could help to identify carriers, which is very important in an X-linked disease. Specific treatment with enzyme replacement therapy (ERT) became available few years ago and improved significantly the natural course of the disease. However, treatment with intravenous ERT has limitations, and the possibility of alternative therapies such as hematopoietic stem cell transplantation and substrate reduction therapy with genistein is being considered. Novel therapies mainly designed to address the CNS manifestations (intrathecal ERT, ERT with fusion proteins, gene therapy and others) are also in development.Expert opinion: The combination of effective therapies with early diagnosis (newborn screening is feasible and could be available shortly) could completely change the prospect for MPS II patients in few years.