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Hunter syndromeBy Mayo Clinic staff
Original Article: http://www.mayoclinic.com/health/hunter-syndrome/DS00790
Hunter syndrome is a rare genetic disorder that occurs when an enzyme your body needs is either missing or doesn't work properly.
Because the body doesn't have enough 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 18 months. It nearly always occurs in males.
There's no cure for Hunter syndrome. Treatment of Hunter syndrome involves management of symptoms and complications.
Hunter syndrome is one type of a group of inherited metabolic disorders called mucopolysaccharidosis (MPS), and Hunter syndrome is referred to as MPS II. Hunter syndrome symptoms vary from person to person. Some people have mild symptoms, while others have severe problems. Symptoms aren't present at birth. If symptoms begin early — around ages 2 to 4 — the syndrome is usually more severe.
Signs and symptoms may include:
- Delayed development, such as late walking or talking
- Changing facial features, including thickening of the lips, tongue and nostrils
- A broad nose and flared nostrils
- Claw-like hands
- A protruding tongue
- 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 damage or loss from degeneration of cells that capture light and buildup of cellular debris in the brain causing pressure on the optic nerve and eye
- Progressive loss of hearing
- Aggressive behavior
- Stunted growth
- Joint stiffness
- Carpal tunnel syndrome
- Sleep apnea
When to see a doctor
Hunter syndrome isn't common, 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 help you decide if you need to see a specialist or seek out further testing.
Hunter syndrome develops when a defective chromosome is inherited from the child's mother. Because of that defective chromosome, an enzyme that's needed to break down complex sugars called glycosaminoglycans is missing or malfunctioning.
The missing or malfunctioning enzyme is called iduronate-2-sulfatase.
In unaffected people, these enzymes are found in parts of the body's cells known as lysosomes. 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 another form of MPS, these enzymes either are missing or don't work correctly.
Normally, the nutrients that are broken down by lysosomes help your body build bone, cartilage, tendons, corneas, skin and connective tissue, and the fluid that lubricates your joints.
When this enzyme isn't working properly, undigested glycosaminoglycans collect in the cells, blood and connective tissues, causing permanent and progressive damage. Hunter syndrome and other forms of MPS are sometimes called lysosomal storage diseases.
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|X-linked recessive inheritance pattern with carrier mother|
There are two major risk factors for developing Hunter syndrome:
- Family history. Hunter syndrome is caused by a defective chromosome, and a child must inherit the defective chromosome to develop the disease. Hunter syndrome is what's known as an X-linked recessive disease. This means that women carry the defective disease-causing X chromosome and can pass it on, but aren't affected by the disease themselves.
- Sex. Hunter syndrome nearly always occurs in males. Girls are less at risk of developing this disease because they inherit 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 male is defective, however, there isn't another normal X chromosome to compensate for the problem.
A variety of complications can occur with Hunter syndrome depending on the type and severity of the disease. These may include:
- Respiratory complications. All forms of MPS, including Hunter syndrome, involve respiratory complications that contribute to your child's disability and sometimes cause death as the disease progresses. An enlarged tongue, thickened gums, and thickening of the nasal passages and windpipe (trachea) make breathing difficult. Children often have chronic ear and sinus infections, respiratory infections, and pneumonia. Sleep apnea, a condition in which breathing is intermittently interrupted during sleep, is often present because of airway constriction.
Cardiac complications. Thickening of tissue associated with Hunter syndrome can cause progressive thickening of the heart's valves. This causes improper closing of heart valves. As a result, the heart and other parts of the body don't receive blood efficiently. As the disease progresses, these conditions often become worse and typically result in heart failure.
The thickening of tissue can also cause narrowing of the aorta (coarctation) and other blood vessels. This in turn can result in high blood pressure (hypertension) and narrowing of arteries in the lungs (pulmonary hypertension).
Skeletal and connective tissue complications. The storage of undigested glycosaminoglycans in connective tissues results in abnormalities in bones, joints and ligaments. This reduces your child's growth, causing pain and physical malformations, and making it difficult for him or her to move.
Nearly everyone with Hunter syndrome experiences joint stiffness, which makes movement painful. The stiffness is caused by swelling of joint connective tissues and abnormalities of cartilage and bones. If your child is in pain, he or she will likely move less, which can lead to more stiffness and pain.
The group of abnormalities typically seen in the bones of people with Hunter syndrome is called dysostosis multiplex. Children with these abnormalities can develop irregularly shaped vertebrae and spines (kyphoscoliosis), ribs, arms, fingers, legs, and pelvises. Their skulls may press down on or fuse with their upper spines. These complications cause many people with Hunter syndrome to be abnormally short. Those with milder cases may reach normal or near-normal height.
Hernias (inguinal and umbilical) are common in Hunter syndrome. They happen because of problems with connective tissue. A hernia occurs when soft tissue, usually part of the intestine, pokes through a weak spot or tear in the lower abdominal wall. Hernias associated with Hunter syndrome can become quite large and are often one of the first signs of the disorder. Enlargement of the liver and spleen (hepatosplenomegaly), which is common in Hunter syndrome, may increase pressure in the abdomen, causing a hernia.
Brain and nervous system complications. A variety of neurological complications may be present and continue to develop in children with Hunter syndrome. Many neurological problems are caused by buildup of excess fluids in your child's brain (hydrocephalus). Pressure from these fluids can cause other problems that may affect your child's eyes and other sensory organs, which can cause severe headaches, interfere with vision and change your child's mental state. Placement of a shunt may help drain excess fluids and relieve pressure on the spinal cord. Imaging tests also may reveal a variety of cyst-like structures in parts of the brain.
Your child also may develop a condition in which the membranes that surround the spinal cord may become thick and scarred (hypertrophic cervical pachymeningitis). This causes pressure and compression of the upper spinal cord. As a result, your child may develop fatigue in his or her legs and gradually weaken and become less physically active.
Other disorders, such as carpal tunnel syndrome, can result from nerve compression that happens because of bone deformities and storage of glycosaminoglycans in tissues.
Abnormal behavior can develop in children with more-severe cases of Hunter syndrome. Often your child's mental development will become affected between the ages of 2 and 6. Some children are hyperactive and have trouble paying attention or following directions. Your child may also behave aggressively and seem unable to sense danger. As your child's overall physical functioning declines, these behavior problems tend to become less severe.
Seizures also may occur in children with Hunter syndrome.
- Longer recovery from other illnesses. Be aware that recovery times from normal childhood illnesses may be longer for children with Hunter and other MPS syndromes. As a result, be sure to take general preventive measures — for example, get your child a flu shot and ensure your child receives all necessary vaccinations.
Preparing for your appointment
You'll probably first bring up your concerns about your child with his or her primary care doctor. Your child's doctor then will likely direct you to specialists for a definitive diagnosis and treatment. However, your child's primary care doctor generally still stays involved to help coordinate your child's health care needs. Some of the specialists that may be involved in your child's care include an ear, nose and throat specialist (otolaryngologist), a heart specialist (cardiologist), a brain and nerve specialist (neurologist), an eye specialist (ophthalmologist), a dietitian, and physical, occupational and speech therapists.
Here's some information to help you get ready for your appointment, and what you might expect from your child's doctor.
What you can do
- Make a list of any signs or symptoms you've noticed in your child, including any that may seem unrelated to Hunter syndrome. For example, diarrhea is a sign of Hunter syndrome, but one that you might not necessarily link to behavioral problems.
- Write down key personal information, including any personal or family history of a genetic disorder.
- Take a family member or friend along, if possible. Sometimes it can be difficult to remember all of the information provided to you during an appointment. Someone who accompanies you may remember something that you missed or forgot.
- Write down questions to ask your doctor.
Preparing a list of questions will help you make sure you cover all of the points that are important to you. Some basic questions you might want to ask your doctor include:
- What is Hunter syndrome?
- Are there any other possible causes for my child's symptoms?
- Are any additional tests needed to confirm the diagnosis?
- What treatments are available, and which ones do you recommend for my child?
- Does this treatment have any risk?
- What type of improvement can we expect?
- What is my child's long-term prognosis?
- Are there alternatives to the primary approach that you're suggesting?
- Does my child need to eat a special diet?
- If my child is in pain, how can I make my child more comfortable?
- What are your suggestions for handling behavioral issues?
- What about routine well-child care? Should my child get routine childhood immunizations? Should my child get flu shots?
- Does my child need to see different specialists?
- What type of help will my child need in school, and how can I ensure that public schools will provide the educational resources my child needs?
- If I have any more children, what's the likelihood that I will pass this syndrome on to them? Can I prevent that from happening?
- Are there any brochures or other printed material that I can take home with me? What websites do you recommend visiting? Are there local resources available for me and my child?
- Can you recommend someone I can speak with about insurance coverage and other expenses related to the special needs of my child?
In addition to the questions that you've prepared to ask your doctor, don't hesitate to ask additional questions that occur to you during your appointment. Don't hesitate to take notes. At the end of your appointment, you may wish to summarize the information you've received with your doctor to make sure you understand it.
What to expect from your doctor
Your doctor is likely to ask you a number of questions. Being ready to answer them may reserve time to go over any points you want to spend more time on. Your doctor may ask:
- When did you first notice your child's symptoms?
- Have other adults mentioned any concerns about your child?
- Are your child's symptoms present all the time or do they come and go?
- Do you know if there is a family history of Hunter syndrome?
- Does anything make your child's symptoms better?
- What, if anything, appears to worsen your child's symptoms?
Tests and diagnosis
Babies born with Hunter syndrome almost always appear healthy at birth. Changes in facial features are often the first noticeable sign that something's not right.
To confirm the diagnosis of Hunter syndrome, your doctor will perform blood, urine or tissue sample tests that look for excess glycosaminoglycans in your child's urine or a deficiency of enzymes in your child's body fluids or cells. In addition, a genetic analysis can confirm the diagnosis.
Sometimes another health issue 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 of the fluid that surrounds the baby (amniocentesis) or of a tissue sample from the placenta (chorionic villus sampling) can verify if your unborn child carries a copy of the defective gene or is affected with the disorder.
Treatments and drugs
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.
Although there's no cure for Hunter or other MPS syndromes, some treatments that are in their early stages have had some success by slowing the disease's progress and lessening its severity.
These emerging treatments include:
- Bone marrow transplantation. If a healthy donor 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.
Enzyme therapy. This treatment uses man-made or genetically engineered enzymes to replace your child's missing or defective enzymes and ease the disease symptoms. Called idursulfase (Elaprase), this treatment is given once a week through an intravenous line. Given early enough, enzyme replacement therapy may delay or prevent some of the symptoms of Hunter syndrome. It's unclear, however, if the improvements seen with this therapy are significant enough to raise quality of life for people with the disease. In addition, benefits in thinking and intelligence haven't been seen with enzyme replacement therapy.
Serious allergic reactions can occur during enzyme replacement therapy. Other possible side effects include headache, fever, skin reactions and high blood pressure. Side effects tend to lessen over time, however.
- Gene therapy. Replacing the chromosome responsible for producing the missing enzyme could theoretically cure Hunter syndrome, but much more research is needed.
Treatments for complications
- 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. Breathing devices that use air pressure to keep the airway open — such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) devices — can help with upper airway obstructions and sleep apnea. Keeping your child's airway open can also help 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. Because most children with Hunter syndrome don't heal well and often have complications after surgery, options are limited 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 stop the progressive decline of joint motion. 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 side effects that can make other complications of the disease, such as respiratory problems, even worse.
- Addressing sleep issues. The sleep patterns of a child with Hunter syndrome become more and more disorganized. 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.
Coping and support
Support for you and your family
The challenges for parents, families and caregivers of children with severe disabilities are great. Joining a support group for parents of children with Hunter syndrome or other MPS syndromes can be a great way to obtain practical information and daily living strategies from other parents in similar situations to your own. Many families often find friendship and encouragement in support groups, as well. Ask your doctor if there's a group in your area.
The intense supervision that may be needed for your child can cause you and other caregivers to become physically, mentally and emotionally exhausted. It's important to get help from other family members and to find other kinds of support. If respite care is available, take advantage of it so that you can have a break and be more effective in the long run to meet the day-to-day challenges of caring for a child with special needs.
Check with your county and state for resources that may be available to you as a parent of a child with special needs.
Letting others know
Due to a narrow airway, people with Hunter syndrome often have difficulty receiving a breathing tube (being intubated) during general anesthesia. You may wish to note this on child care or school forms so that emergency personnel can be alerted to this fact, in case your child has an emergency and you're not there. An experienced anesthesia specialist (anesthesiologist) should perform the intubation of a person with Hunter syndrome.
Hunter syndrome is a genetic disorder. Talk to your doctor or a genetic counselor if you're thinking about having children and you or any members of your family have a genetic disorder or a family history of genetic disorders. If you think you might be a carrier, genetic tests are available. If you already have a child with Hunter syndrome, you may wish to seek the advice of a doctor or genetic counselor before you have more children.
- Scarpa, et al. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet Journal of Rare Diseases. 2011;6:1.
- Martin R, et al. Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics. 2008;121:e377.
- Mucopolysaccharidoses fact sheet. National Institute of Neurological Disorders and Stroke. http://www.ninds.nih.gov/disorders/mucopolysaccharidoses/detail_mucopolysaccharidoses.htm. Accessed Oct. 11, 2012.
- Kakkis E, et al. Complications and management of the mucopolysaccharidoses. http://www.uptodate.com/ index. Accessed Sept. 21, 2012.
- Muenzer J, et al. Multidisciplinary management of Hunter syndrome. Pediatrics. 2009;124:e1228.
- Da Silva EMK, et al. Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome). Cochrane Database of Systematic Reviews. 2011; 9:CD008185. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008185.pub2/abstract. Accessed Oct. 1, 2012.
- Valayannopoulos V, et al. Therapy for the mucopolysaccharidoses. Rheumatology. 2011;50:v49.