Published: 18 Jun 2025

ICD9: 277.5      ICD10: E76.3      ICD11: 5C56.3

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare, inherited genetic disorder that primarily affects males.
It's a lysosomal storage disease, meaning it's caused by a deficiency of a specific enzyme that's responsible for breaking down complex sugar molecules called glycosaminoglycans (GAGs), also known as mucopolysaccharides. These GAGs build up in cells, tissues, and organs throughout the body, causing progressive damage.

Here's a more detailed breakdown:

Lysosomal Storage Disease: Lysosomes are organelles within cells that act as the recycling centers. They contain enzymes to break down various molecules. In lysosomal storage diseases, a specific enzyme is deficient or absent, leading to the accumulation of undigested material within the lysosome.

Enzyme Deficiency: Hunter syndrome is caused by a deficiency of the enzyme iduronate-2-sulfatase (I2S). The gene that codes for this enzyme is located on the X chromosome.

Glycosaminoglycans (GAGs) Buildup: Because the I2S enzyme is deficient, the GAGs dermatan sulfate and heparan sulfate accumulate. This buildup interferes with the normal functioning of cells, tissues, and organs.

Inheritance Pattern: Hunter syndrome is X-linked recessive. This means that the gene carrying the mutation is on the X chromosome. Since males have only one X chromosome (XY), if they inherit the mutated gene, they will have the disease. Females have two X chromosomes (XX). If they inherit one mutated gene, they are usually carriers but generally do not have the full-blown disease because their other X chromosome usually provides a working copy of the gene. However, some females may experience mild symptoms.

Symptoms and Severity: The severity of Hunter syndrome varies. There are generally considered to be two forms:

Severe (Classical) Hunter Syndrome: Symptoms typically appear between 2 and 4 years of age and progress rapidly. Individuals with the severe form usually have significant intellectual disability, and a shortened lifespan (often into the teens).

Attenuated (Mild) Hunter Syndrome: Symptoms may be milder and appear later in childhood or even adulthood. Intellectual disability is less common or may be mild. Individuals with the attenuated form may live into adulthood.

Common Symptoms: Symptoms can vary but often include:

Skeletal abnormalities: Stiff joints, short stature, claw-like hands, scoliosis (curvature of the spine).
Facial features: Coarse facial features, enlarged tongue.
Organ involvement: Enlarged liver and spleen (hepatosplenomegaly), heart problems, respiratory problems due to airway obstruction and lung disease.
Cognitive impairment: Varying degrees of intellectual disability (more common in the severe form).
Skin findings: Pebbly skin lesions (papules) on the upper back and upper arms.
Hearing loss: Common.
Hernias: Inguinal and umbilical hernias are common.

Diagnosis: Hunter syndrome is diagnosed through:

Enzyme assay: Measures the level of I2S enzyme activity in blood or fibroblasts (skin cells).
Urine test: Measures the levels of GAGs (dermatan sulfate and heparan sulfate) in the urine.
Genetic testing: Identifies mutations in the *IDS* gene (the gene that codes for I2S).

Treatment: There is no cure for Hunter syndrome, but treatments can help manage the symptoms and improve the quality of life:

Enzyme Replacement Therapy (ERT): Weekly infusions of a synthetic I2S enzyme (idursulfase) can help reduce the buildup of GAGs in some tissues and organs. It can improve some symptoms but does not cross the blood-brain barrier, so it doesn't directly address cognitive issues.
Hematopoietic Stem Cell Transplantation (HSCT): Stem cell transplants (bone marrow or umbilical cord blood transplant) can provide a source of healthy cells that produce the missing enzyme. HSCT is most effective when performed early in the course of the disease. It carries significant risks.
Symptomatic treatment: Managing specific symptoms (e.g., heart problems, respiratory issues) with medication, surgery, and supportive care. This may include physical therapy, occupational therapy, and speech therapy.

Research: Research is ongoing to develop new and improved treatments for Hunter syndrome, including gene therapy and novel enzyme therapies.

In summary, Hunter syndrome is a serious genetic disorder caused by a deficiency in a specific enzyme needed to break down complex sugars. This deficiency leads to a buildup of these sugars in the body, causing a range of symptoms that can significantly impact a person's health and quality of life. Early diagnosis and appropriate treatment are crucial for managing the disease and improving outcomes.