Mucopolysaccharidosis type II (MPS II), commonly known as Hunter syndrome.
Itis a rare, inherited lysosomal storage disorder.
It is caused by a deficiency of the enzyme iduronate-2-sulfatase (I2S).
This deficiency leads to a harmful buildup of complex sugar molecules called glycosaminoglycans (GAGs) in cells, tissues, and organs throughout the body.
Genetic Mutation: Caused by changes or mutations in the IDS gene.
Inheritance Pattern: Follows an X-linked recessive pattern, meaning it affects almost exclusively males because they have only one X chromosome.
Symptoms typically do not appear at birth, becoming noticeable between ages 2 and 4.
The condition is divided into two primary forms:
Severe (Neuropathic) Form: Involves progressive cognitive decline and developmental regression around ages 4 to 8, with a shortened life expectancy typically into the second decade of life.
Attenuated (Non-Neuropathic) Form: Intelligence is unaffected, and individuals can survive into adulthood.
Common Physical Signs: Coarse facial features, enlarged head (macrocephaly), a deep hoarse voice, umbilical or inguinal hernias, enlarged liver and spleen (hepatosplenomegaly), airway obstruction, and joint stiffness.
Diagnosis: Confirmed via urine GAG screening followed by an enzymatic assay measuring I2S activity in leukocytes or blood, alongside genetic testing.
Treatment: Primarily involves weekly intravenous enzyme replacement therapy (ERT) with recombinant idursulfase to help manage physical symptoms and improve endurance, though standard ERT does not cross the blood-brain barrier to treat neurological symptoms.
Supportive and palliative care address airway, cardiac, and joint complications.
Intravenous enzyme replacement therapy, ameliorates systemic manifestation of MPSII but it fails to prevent neurocognitive decline owing to limited penetration of the blood brain barrier.
Tividenofusp alpha a fusion iduronate 2 sulfatase with a transferrin receptor binding domain overcomes this limitation and enables enzymes delivery to both brain and peripheral tissues.
Tividenofusp alpha reduces sustained reductions in CSF and urinary heparan sulfate levels to near normal values as well as decreased serum neurofilament light chain levels, indicating preserved neuronal integrity.
Cognitive adaptive function, stabilized, or improved with this agent.