Hunter syndrome

Hunter syndrome is a hereditary disease in which the breakdown of a mucopolysaccharide (a chemical that is widely distributed in the body outside of cells) is defective. This chemical builds up and causes a characteristic facial appearance, abnormal function of multiple organs, and in severe cases, early death.

Hunter syndrome is inherited as an X-linked recessive disease. This means that boys will be the ones most often affected, because the defective gene is on the X chromosome. Boys have only 1 copy of the X chromosome. Girls have 2 copies.

Because girls have two X chromosomes, their normal copy on one X can provide a functioning gene, even if their other X has the abnormal gene. Women can carry the defective gene and pass it on, without being affected themselves, unless both their copies are abnormal. But because boys have an X and a Y, there is no normal X gene to fix the problem if the X is defective.

The metabolic abnormality that causes Hunter syndrome is a lack of the enzyme iduronate sulfatase. Without this enzyme, mucopolysaccharides collect in various body tissues, causing damage.

Affected children may develop an early-onset type (severe form) shortly after age 2 that causes a large skull, coarse facial features, profound mental retardation, spasticity, aggressive behavior, joint stiffness, and death before age 20. A late-onset type (mild form) causes later and less severe symptoms.

Juvenile form (early-onset, severe form):

• Mental deterioration
• Severe mental retardation
• Aggressive behavior
• Hyperactivity

Late (mild) form:

• Mild to no mental deficiency

Both forms:

• Coarse facial features
• Large head (macrocephaly)
• Stiffening of joints
• Increased hair (hypertrichosis)
• Deafness (progressive)
• Enlargement of internal organs such as liver and spleen
• Abnormal retina (back of the eye)
• Carpal tunnel syndrome

Signs of the disorder that the doctor might look for include:

• Hepatomegaly (enlargement of liver)
• Splenomegaly (enlargement of spleen)
• Inguinal hernia
• Spasticity
• Heart murmur and leaky heart valves
• Joint contractures
• Excretion of heparan sulfate and dermatan sulfate in urine
• Decreased iduronate sulfatase enzyme activity in serum or cells

• Urine for heparan sulfate and dermatan sulfate
• Enzyme study, decreased iduronate sulfatase (may be studied in serum, white blood cells, skin cells)
• Genetic testing may show mutation in the iduronate sulfatase gene

The U.S. Food and Drug Administration has approved the first treatment for Hunter syndrome. The medicine, called idursulfase (Elaprase), is given through a vein (intravenously). Talk to your doctor for more information.

Bone marrow transplant has been tried for the early-onset form with variable results.

Individual problems should be addressed separately.

Life expectancy for the early-onset (severe) form is 10 - 20 years. Life expectancy for the late-onset (mild) form is 20 - 60 years.

• Airway obstruction in late-onset (mild) form
• Worsening mental deterioration in early-onset (severe) form
• Worsening loss of activities of daily living in early-onset (severe) form
• Worsening hearing loss in both mild and severe forms
• Worsening joint stiffness leading to contractures of joints in early-onset (severe) form
• Carpal tunnel syndrome

Call your health care provider if you or your child manifest a group of these symptoms, or if you know you are a genetic carrier and are considering having children.

Genetic counseling is recommended for prospective parents with a family history of Hunter syndrome. Prenatal testing is available. Carrier testing for female relatives of affected males is available at a few specialized centers.

Muenzer J, Wraith JE, Beck M, et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73.