Hunter Syndrome: Symptoms, Causes, Diagnosis & Treatment

Hunter syndrome, also known as mucopolysaccharidosis type II (MPS II), is a rare genetic condition caused by the absence of an enzyme called iduronate-2-sulfatase. Without this enzyme, certain complex sugars build up inside the body, which gradually affects many organs. Because the condition is linked to the X chromosome, it mainly affects boys.

The symptoms of hunter syndrome can vary from person to person. Some children experience changes in learning and behavior, while others have mostly physical symptoms such as joint stiffness, hearing problems, enlarged organs, or heart issues. These signs usually appear in early childhood and tend to progress over time.

Treatment options depend on the severity of the condition and may include enzyme replacement therapy, supportive care, or newer treatment approaches still being studied. Since early diagnosis can improve long-term outcomes, many regions now include Hunter syndrome in newborn screening programs.

Main symptoms

Common symptoms of Hunter syndrome include:

• Coarse facial features

• Enlarged liver or spleen

• Frequent ear infections

• Hearing loss

• Joint stiffness or limited movement

• Thickened skin

• Hernias

• Heart valve problems

• Developmental delay or loss of skills in the neuronopathic form

• Behavioral changes such as hyperactivity

Symptoms may differ depending on whether the child has the neuronopathic or non-neuronopathic form of the condition.

Possible causes

Hunter syndrome is caused by changes in the IDS gene, which provides instructions for making the iduronate-2-sulfatase enzyme. When the enzyme is missing or not working well, glycosaminoglycans such as dermatan sulfate and heparan sulfate build up inside cells.

Hunter syndrome follows an X-linked recessive inheritance pattern. Boys are usually affected because they have only one X chromosome. Girls may be carriers, although some may develop symptoms if one X chromosome is more active than the other.

Confirming a diagnosis

Diagnosis usually begins with urine testing to look for high levels of glycosaminoglycans. This is followed by enzyme testing to measure iduronate-2-sulfatase activity. Genetic testing can confirm changes in the IDS gene.

In the United States, Hunter syndrome has been added to the Recommended Uniform Screening Panel, which allows newborn screening programs to identify affected infants earlier in life.

Treatment options

The treatment for hunter syndrome can involve several approaches depending on the child’s needs.

1. Enzyme replacement therapy

Enzyme replacement therapy with idursulfase helps reduce the buildup of glycosaminoglycans. Studies show improvements in walking ability, lung function, liver size, and heart measurements, especially when treatment begins early.

2. Intrathecal enzyme therapy

For children with symptoms that affect the brain, intrathecal forms of idursulfase are being studied. This treatment delivers the enzyme directly into the spinal fluid. Early results suggest possible benefits for cognitive function.

3. Hematopoietic stem cell transplantation

Stem cell transplantation has been explored as a treatment option. It may help slow neurological progression when performed very early, although outcomes can vary.

4. Emerging therapies

Ongoing research includes brain-targeting enzyme treatments, fusion proteins designed to cross the blood brain barrier, and gene therapy approaches. Some clinical trials aim to provide long-lasting enzyme production through modified stem cells.

Prevention measures

There is currently no way to prevent hunter syndrome. Genetic counseling can help families understand how the condition is inherited and whether carrier testing might be useful. Newborn screening also supports early diagnosis and treatment planning, which can improve long-term outcomes