HUNTER SYNDROME

• DEFINITION

Hunter syndrome is a rare genetic disorder that occurs when an enzyme your body needs is either missing or malfunctioning.

Because the body doesn't have adequate supplies of the enzyme to break down certain complex molecules, the molecules build up in harmful amounts in certain cells and tissues. The buildup that occurs in Hunter syndrome eventually causes permanent, progressive damage affecting appearance, mental development, organ function and physical abilities.

Hunter syndrome appears in children as young as age 2. It nearly always occurs in males, although it may occur in females.

Treatment of Hunter syndrome mostly involves management of your symptoms and complications. Enzyme replacement therapy and other emerging therapies may offer more help in the future.

• SYMPTOMS

Hunter syndrome is one type of a group of inherited metabolic disorders called mucopolysaccharidosis (MPS), and Hunter syndrome is referred to as MPS II. There are two subtypes of Hunter syndrome, MPS IIA and MPS IIB. Symptoms vary according to subtype.

Type MPS IIA (early onset)
Early-onset Hunter syndrome (MPS IIA) is the more severe of the two types and usually appears around age 2 and up to age 4. This form of the disorder may result in profound mental retardation by late childhood. Children with this form of the syndrome usually don't survive beyond their teens.

Signs and symptoms of MPS IIA include:

• A decline in development, which usually appears between ages 1 1/2 and 3, followed by a progressive loss of skills
• Coarse facial features, including thickening of the lips, tongue and nostrils
• Abnormal bone size or shape and other skeletal irregularities
• Enlarged internal organs, such as the liver and spleen, resulting in a distended abdomen
• Respiratory difficulties including sleep apnea, a condition in which breathing intermittently stops during sleep
• Cardiovascular disorders, such as progressive thickening of heart valves, high blood pressure (hypertension) and obstruction of blood vessels
• Vision loss or impairment from degeneration of cells that capture light and buildup of cellular debris in the brain causing pressure on the optic nerve and eye
• Skin lesions on the back and upper arms
• Progressive loss of hearing
• Aggressive behavior
• Stunted growth
• Joint stiffness
• Diarrhea

Type MPS IIB (late onset)
Late-onset Hunter syndrome (MPS IIB) is milder and causes less severe symptoms that appear much later. This form is usually diagnosed after age 10, and may not be detected until adulthood. Intellectual and social development usually is nearly normal, but the condition may affect verbal and reading skills. People with this type of Hunter syndrome can live into their 50s.

Signs and symptoms of MPS IIB include:

• Abnormal bone size or shape and other skeletal irregularities, but less severe than in MPS IIA
• Somewhat stunted growth
• Poor peripheral vision
• Joint stiffness
• Hearing loss
• Diarrhea
• Sleep apnea

When to see a doctor
Hunter syndrome isn't a common disorder, but if you notice changes in your child's facial appearance, a loss of previously acquired skills, or other signs or symptoms listed above, talk to your child's primary care doctor. He or she can perform an evaluation and help you decide if you need to see a specialist or seek out further testing.

• CAUSES

As with all types of MPS, Hunter syndrome is caused when a person lacks a specific enzyme his or her body needs to break down glycosaminoglycans — molecules formed from long chains of complex carbohydrates.

In unaffected people, these enzymes are found in cell components called lysosomes. Lysosomes break down the complex carbohydrates into nutrients, such as proteins and simpler molecules so that your body can use them at the cellular level. These nutrients help your body build bone, cartilage, tendons, corneas, skin and connective tissue, and are also found in the fluid that lubricates your joints. MPS disorders are also referred to as lysosomal storage disorders.

The lysosomes use enzymes to break down glycosaminoglycans, as part of the body's normal recycling and renewal process. In a person with Hunter syndrome or other form of MPS, these enzymes either are missing or don't work correctly.

These breaking-down tasks involve 11 different enzymes, and the particular enzyme that is missing or malfunctioning largely determines the type of MPS disorder. As a result of these enzyme malfunctions, undigested glycosaminoglycans collect in the cells, blood and connective tissues, causing permanent and progressive damage. In the case of Hunter syndrome, the missing or malfunctioning enzyme is called iduronate-2-sulfatase.

• RISK FACTORS

The risk of an unborn child acquiring Hunter syndrome is determined by the genetics of the child's mother.

Hunter syndrome is an X-linked recessive disease. This means that women carry the disease and pass it on — most often to their sons — but the mothers aren't affected by the disease themselves. Hunter syndrome is the only type of MPS that can be passed on by a defective gene in the mother alone. In all other types of MPS, the child inherits the syndrome because the same defective gene has been passed on by both parents.

In an X-linked recessive disorder, the mutated gene is located on the X chromosome. In this case, the mother is a carrier, which means she has one mutated gene and one normal gene for the condition.

Girls are less at risk of inheriting this disease because they have two X chromosomes. If one of the X chromosomes is defective, their normal X chromosome can provide a functioning gene. If the X chromosome of a boy is defective, however, there isn't another normal chromosome to compensate for the problem.

A man with an X-linked recessive disorder will pass his normal Y gene to his sons, and none will be affected. He will pass his mutated X gene to his daughters, and they will be carriers. These chances are the same in each pregnancy.

If you have a child with Hunter syndrome or other MPS syndrome, talk to your doctor or a genetic counselor before planning to have more children. If you're a sister or aunt of a person with Hunter syndrome, you may also be a carrier. There are tests for genetic carriers, so you may wish to seek genetic counseling before having children.

• TESTS & DIAGNOSIS

Confirmation of a diagnosis of Hunter syndrome requires tests performed on blood, urine or tissue samples. Your doctor will look for excess glycosaminoglycans in your child's urine or a deficiency of enzymes in your child's body fluids or cells.

Sometimes secondary health issues can lead to a diagnosis of Hunter syndrome. For example, if your child has recurrent pneumonia, a chest X-ray may show irregularly shaped vertebrae and ribs, a common sign of this syndrome. This finding could lead to further testing and an earlier diagnosis of the disease. However, because the disorder progresses slowly and its signs and symptoms overlap with a number of other disorders, definitive diagnosis may take some time.

Prenatal testing
Prenatal testing of the fluid that surrounds the baby (amniocentesis) or taking a tissue sample from the placenta (chorionic villus sampling) can verify if your child carries a copy of the defective gene or is affected with the disorder.

• TREATMENTS

Because there's no cure for Hunter syndrome, treatment focuses on managing signs, symptoms and complications to provide some relief for your child as the disease progresses. Treatment may involve the following:

• Relief for respiratory complications. Removal of tonsils and adenoids can open up your child's airway and relieve sleep apnea. But as the disease progresses, tissues continue to thicken and these problems can come back. Some types of breathing devices can help with upper airway obstructions and sleep apnea. Keeping your child's airway open can also avoid low blood oxygen levels (hypoxemia).
• Addressing heart complications. Your child's doctor will want to watch closely for cardiovascular complications, such as high blood pressure, heart murmur and leaky heart valves. If your child has severe cardiovascular problems, your doctor may recommend surgery to replace heart valves.

• Treatment for skeletal and connective tissue problems. Most children with Hunter syndrome don't heal well and often have complications from surgery. That limits options for addressing skeletal and connective tissue complications. For example, surgery to stabilize the spine using internal hardware is difficult when bones are fragile.

  Your child's joint flexibility can be improved with physical therapy, which helps address stiffness and maintain function. However, physical therapy can't prevent the progressive decline of mobility. Your child may eventually need to use a wheelchair because of pain and limited stamina.

  Surgery can repair hernias, but because of weakness in connective tissues, results usually aren't ideal. The procedure often needs to be repeated. One option is to manage your child's hernias with supportive trusses rather than surgery because of the risks of anesthesia and surgery.

• Managing neurological complications. Problems associated with the buildup of fluid and tissue around the brain and spinal cord are difficult to address because of the inherent risks in treating these parts of the body. Your child's doctor may recommend surgery to drain excess fluids or remove built-up tissue.

  If your child has seizures, your doctor may prescribe anticonvulsant medications.

• Managing behavioral problems. If your child develops abnormal behavior as a result of Hunter syndrome, providing a safe home environment is one of the most important ways you can manage this challenge. Treating behavior problems with medications has had limited success because most medications have negative effects on other manifestations of the disease.
• Addressing sleep issues. The sleep patterns of a child with Hunter syndrome become more and more disorganized, causing some children to be active around the clock. Medications including sedatives and especially melatonin can improve sleep. Keeping a strict bedtime schedule and making sure your child sleeps in a well-darkened room also can help. In addition, creating a safe environment in your child's bedroom — putting the mattress on the floor, padding the walls, removing all hard furniture, placing only soft, safe toys in the room — may help you rest easier if you know your child has less opportunity for injury.

Treatments in development
Although there's no cure for Hunter or other MPS syndromes, some treatments that are in their early stages have had some success in altering the natural course of the disease to slow its progress and lessen its severity.

These emerging treatments include:

• Bone marrow transplantation. If a healthy donor is found that matches your child's blood and tissue type, bone marrow transplantation can be used to treat some symptoms in milder forms of Hunter syndrome. Bone marrow is taken from the hip of the donor and transplanted to your child by injecting it into his or her veins (intravenously). This treatment can help ease the problems of breathing; mobility; and heart, liver and spleen function. It can also help prevent your child's mental regression. This treatment won't help with bone or vision problems.
• Cord blood transplantation. This treatment uses umbilical cord blood from an unrelated donor that's collected at the time of the donor's birth. The cord blood is transplanted intravenously. This treatment is designed to help your child's bone marrow and enzyme activity recover. It can also reduce the effects of the disease on facial and skin features, joint mobility, hearing, and enlargement of the liver and spleen.
• Enzyme therapy. This treatment uses man-made or genetically engineered enzymes, which are injected directly into your child's bloodstream to replace your child's missing or defective enzymes and ease the disease symptoms. The Food and Drug Administration gave its approval in July 2006 for the first human enzyme replacement therapy for Hunter syndrome. People involved in tests of the drug idursulfase (Elaprase) showed improvement in their ability to walk after a year of weekly treatments. The infusion has produced severe allergic reactions in some people, so your doctor will monitor your child closely if this treatment is chosen.

These therapies show promise, but they don't provide a cure. More research is needed.