What is Hunter syndrome

Hunter syndrome, or Mucopolysaccharidosis type II (MPS II), is a rare, life-limiting genetic disorder caused by the body's inability to break down complex sugar molecules called glycosaminoglycans (GAGs). This leads to the progressive accumulation of GAGs in tissues and organs throughout the body, resulting in significant multisystem health challenges.

What causes Hunter syndrome?

Hunter syndrome occurs due to a deficiency or total absence of the enzyme iduronate-2-sulfatase (I2S). Without this enzyme, GAGs build up in lysosomes, the "recycling centers" of cells, causing them to malfunction. This condition is inherited in an X-linked recessive pattern, meaning it primarily affects males, as they inherit the single X chromosome carrying the mutation from their mothers.

Which body systems are affected by Hunter syndrome?

Because GAGs are found throughout the body, Hunter syndrome is a multisystemic disease. The accumulation of these molecules can lead to:

• Physical features: Enlarged head (macrocephaly), coarse facial features, and thick skin.


• Skeletal system: Joint stiffness, restricted range of motion, and bone abnormalities.


• Internal organs: Enlarged liver and spleen (hepatosplenomegaly) and heart valve thickening.


• Respiratory and ENT: Frequent ear infections, hearing loss, and airway obstruction.


• Neurological (in severe cases): Developmental delays and progressive cognitive decline.

How common is Hunter syndrome?

Hunter syndrome is extremely rare, with an estimated prevalence of approximately 1 in 100,000 to 1 in 170,000 live male births. While it can occur in any ethnic group, it is categorized clinically into two primary forms: the severe (neuronopathic) form and the attenuated (non-neuronopathic) form. The severe form typically presents between ages 2 and 4, whereas the attenuated form may not be diagnosed until later in childhood or adolescence.

How does Hunter syndrome differ from other lysosomal storage disorders?

While Hunter syndrome shares clinical features with other mucopolysaccharidoses (such as Hurler syndrome), it is unique due to its X-linked inheritance pattern. Unlike other MPS types which are autosomal recessive, Hunter syndrome is the only type of MPS that follows this specific gender-linked inheritance, distinguishing it in both genetic counseling and family planning discussions.

Next steps

• Consult with a metabolic specialist or clinical geneticist to confirm a diagnosis via enzyme assay or genetic testing.


• Join our DiseaseMaps.org community, where 66 people with Hunter syndrome have shared their experiences and insights.


• Connect with the National MPS Society or the MPS Society UK for specialized support resources.


• Discuss potential enzyme replacement therapies (ERT) or clinical trials with your care team.

Medical disclaimer: This content is for informational purposes only and does not constitute professional medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Hunter syndrome


• Orphanet: Mucopolysaccharidosis type II


• OMIM (Online Mendelian Inheritance in Man): Mucopolysaccharidosis type II


• National MPS Society: Information on MPS II