Hunter syndrome

Hunter's syndrome is a mucopolysaccharide disease caused by the enzymatic deficiency of iduronate-2-sulfatase (I2S). This is also called as mucopolysaccharoidosis Type II. It was first described by Scottish physician Charles A. Hunter (1873-1955) in 1917.

Definition

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.

Causes, incidence, and risk factors

Hunter syndrome is inherited as an X-linked recessive disease. This means that women carry the disease and can pass it on to their sons, but are not themselves affected.

Because girls have two X chromosomes, their normal X can provide a functioning gene even if their other X is defective. 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-2-sulfatase. In its absence, 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.

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 and tests

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 heart valve dysfunction
• joint contractures
• excretion of heparan sulfate and dermatan sulfate in urine
• decreased iduronate sulfatase enzyme activity in serum or cells

Tests that may indicate this disorder is present include:

• urine for heparan sulfate and dermatan sulfate
• enzyme study, decreased iduronosulfate sulfatase (may be studied in serum, white blood cells and fibroblasts)
• genetic testing may show mutation in the iduronate sulfatase gene

Treatment

There is no cure for Hunter syndrome. A specific treatment is being developed called enzyme replacement therapy . However, it is experimental and may not be able to prevent neurologic disease from getting worse. Individual problems should be addressed separately. Bone marrow transplant has been attempted for the early-onset form with variable results.

Prognosis

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

Complications

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

Prevention

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.

See also

• Genetic counseling
• Prenatal testing

External links

• Hunter Syndrome. About.
• Hunter Syndrome Patient/Family Resources. CCHS Resources.
• Charles A. Hunter. WhoNamedIt.

Source

• Hunter Syndrome. Medline Plus.

Reference

• Hunter CA: A rare disease in two brothers. Proceedings of the Royal Society of Medicine, London, 1917, 10: 104-116