At present, Hurler syndrome is considered to be incurable, since, for a cure, replacement of the faulty gene with a normal one in nearly all the cells in the body would most likely be required. This is a theoretical possibility, and research investigating the feasibility of this approach is ongoing. However, this type of treatment is not currently available as an option for Hurler syndrome.
There are currently two different well-established approaches to the treatment of Hurler syndrome. Both approaches involve supplying children with the alpha-L iduronidase enzyme that they need in order to break down excess glucosaminoglycans that are responsible for the syndrome's complications.
One approach to accomplish this consists of supplying the missing alpha-L-iduronidase enzyme in the form of a drug, which must be regularly injected. This type of approach is called enzyme replacement therapy. Enzyme replacement therapy may improve a child's problems with growth and bone development, breathing, joints, and heart complications. However, there is little evidence that it has any effect on neurological complications and mental development.
The second approach to supplying the missing enzyme is to provide the child with normal bone marrow cells, donated from a healthy individual. This type of procedure is called bone marrow transplantation (BMT). In BMT, the child's own bone marrow cells are destroyed, and replaced with those from a healthy donor. These foreign bone marrow cells then provide a source of the missing enzyme. BMT is the only procedure currently available that has been shown to be capable of halting the progression of neurological complications, as well as many of the other complications associated with Hurler syndrome. Several studies have also shown significant improvement in tests of mental abilities in some children following BMT. However, regardless of whether enzyme replacement therapy, BMT, or both, are utilized, early diagnosis and treatment are essential, since it is difficult or impossible for any form of treatment to reverse damage already done during a child's development.
Enzyme replacement therapy
Aldurazyme® (laronidase), a man-made version of the deficient alpha-L-iduronidase enzyme, has been approved by the U.S. Food and Drug Administration (FDA) for use in therapy for Hurler syndrome. The enzyme is administered weekly, by slow injection (infusion), into a vein. The procedure for laronidase infusion takes several hours and must be performed weekly. Significant improvement in lung function and walking ability in children with Hurler syndrome after long-term treatment with laronidase has been reported. However, laronidase administered by intravenous infusion cannot enter the brain, since the brain is normally protected by mechanisms that prevent entry of drugs and other foreign substances from the bloodstream. Therefore, improvement in brain and central nervous system functioning is neither observed nor expected. Direct injection of laronidase into the brain has also been attempted, with promising results, but this treatment remains experimental.
Risks of enzyme replacement therapy:
There are many uncomfortable, but relatively non-serious side effects associated with the infusion procedure, including flushing, fever, headache, nausea, and rash. The most frequently reported side effects of laronidase are chills, vomiting, nausea, rapid heartbeat, blood pressure increase, and decreased amounts of oxygen in the blood. Other possible side effects include upper respiratory tract infection and soreness at the injection site.
There are also some serious and potentially life-threatening allergic reactions associated with this type of intravenous infusion, the most serious of which is called anaphylaxis. Anaphylaxis is a severe allergic reaction to the drug, or, in some cases, to other components in the infusion mixture. Anaphylaxis may result in constriction of the narrow air passages in the lungs, resulting in loss of the ability to breath. This may happen within minutes after the drug is administered, unless emergency treatment is available. Thus, laronidase infusion is usually performed in a hospital or clinic. Patients are also generally given anti-fever drugs and antihistamines immediately prior to the infusion to help reduce complications caused by these types of reactions.
Bone marrow transplantation (BMT)
In bone marrow transplantation (BMT), the child's own bone marrow cells are destroyed by drugs and/or radiation, and replaced with those from a healthy donor. Radiation treatments are typically performed with the patient lying on his or her side. They take about 30 minutes, and are administered twice a day for several days prior to the BMT. The radiation treatment itself is painless. BMT may require up to six months in the hospital. Drugs that are used to destroy the patient's own bone marrow cells are called cytotoxic, or "cell-killing" drugs. Many of these drugs are the same as those used to kill cancer cells, and may include busulfan, melphalan, or methotrexate. After the patient's own bone marrow cells are destroyed using these treatments, the patient is supplied with new bone marrow cells from one of two different sources.
One possible source of normal bone marrow cells is a healthy adult donor. In order to reduce the possibility of rejection reactions and to maximize the chances that the donor's cells will be able to function in their new environment, it is usually best if the donor is a close family member. The donor's cells are injected into a vein, and then migrate to the child's bone marrow, where they divide and replace the child's own defective cells.
Another possible source of normal bone marrow cells is cord blood from an unrelated donor. Cord blood cells are cells obtained from a newborn's blood present in the umbilical cord after birth. Since cells from cord blood banks are now widely available, it is generally possible to find a "match" of the correct tissue type. This type of matching is necessary to enable the new bone marrow cells to function, and to reduce the possibility of rejection reactions. When injected into a vein, cord blood cells are capable of migrating to the bone marrow, dividing, and replacing the child's own defective bone marrow cells. Immune cells called macrophages are present in most tissues in the body. These cells are normally produced in the bone marrow, and then migrate into many different kinds of tissues throughout the body. Macrophages derived from the transplanted bone marrow are believed to be the main source of alpha-L-iduronidase that leads to clinical improvement after BMT in Hurler syndrome. The choice of whether to use cord blood cells from a blood blank, or to use bone marrow cells obtained from a healthy relative, is determined by the availability of a suitable donor, and how close of a "match" to the patient's tissue type can be found.
In some children with Hurler syndrome who received a BMT, there was improvement in hearing, reduction in size of the abnormally large spleen and liver, improvement in lung functioning, and improvement of nervous system abnormalities. In some cases, there was also improvement in mental functioning and learning ability. Thus, in some, but not all, Hurler syndrome patients receiving BMT at a sufficiently early age, the possibility for long term survival is considered good. However, vision problems associated with corneal clouding and bone development abnormalities cannot be reversed by BMT. Surgical treatment for those problems is therefore often necessary.
Risks of BMT: BMT is a highly complex and specialized medical procedure that requires advanced preparation for several common, but life threatening reactions. Graft-versus-host disease (GVHD) is a very common risk of BMT. In GVHD, the foreign bone marrow cells or cord blood cells from the donated marrow or cord blood (the graft) attack and damage the tissues of the transplant patient (the host). GVHD may affect many different parts of the body. The skin, eyes, stomach, and intestines are affected most often. GVHD can range from mild to life-threatening. GVHD can occur with any BMT, except when the donor is an identical twin. Drugs that suppress the immune system, such as corticosteroids, cyclosporine, and methotrexate may be used to try to halt GVHD, but these often have severe side effects, and can interfere with wound healing and normal immune defenses.
Another major risk of BMT is graft failure, which is the term applied to any situation in which the donor cells fail to grow, and therefore cannot make new blood cells required for survival. Thus, graft failure may be life-threatening. Moreover, if the child's own cells were not successfully killed off during the preparatory drug and/or radiation treatments, then these enzyme-deficient cells may begin to re-grow in the bone marrow, as if there had been no transplant. In that case, the child may survive, but the progression of the disease would resume, and continue to worsen. Thus, graft failure is considered to carry a more significant risk for children being treated for Hurler syndrome than for many other diseases that are also treated using BMT.
In addition, because BMT may disrupt the blood clotting mechanism, another potentially fatal risk of BMT is internal bleeding from the lungs.
All of these risks occur frequently, and must therefore be weighed carefully. A child's age, severity of signs and symptoms, and their individualized progression of disease complications must all be considered, before BMT is attempted in any particular case.
Surgery for complications
Surgery to remove tonsils and adenoids, which are the immune tissues in the back of the throat, may improve breathing among affected individuals with obstructive airway disorders and abnormal breathing during sleep. Sleep studies can assess airway status and the possible need for nighttime oxygen. Some patients may require surgical insertion of a tube into the windpipe to aid breathing. Surgery may also be required to correct hernias, and to help drain excessive cerebrospinal fluid from the brain. Surgical intervention may also be beneficial to free nerves and nerve roots trapped as a result of skeletal and other developmental abnormalities. Corneal transplants may improve vision among patients with significant corneal clouding. However, surgery in Hurler syndrome patients often presents special problems for anesthesiologists, since abnormalities in breathing may prevent the utilization of standard anesthetic procedures.
Advice for caregivers
Because the complications of Hurler syndrome may vary widely from one person to the next, and because those complications may be severe, it is essential for a variety of specialists to be involved in the care and treatment of a child with this type of disorder. Thus, in addition to the primary care physician, physical therapists, orthopedic surgeons, otolaryngologists, ophthalmologists, neurologists, cardiologists, lung specialists, dentists, psychiatric specialists, social workers, and parents play a role in the care and management of children with this condition.
Parents of children with Hurler syndrome can obtain up-to-date, detailed information about caring for their children from the National MPS Society. This organization provides regular newsletters and can direct parents and caregivers to the appropriate sources for knowledgeable, experienced help with family support issues, new therapies, clinical trials, and other topics that might help them better cope with the many complex tasks associated with the social as well as medical aspects of caring for a child with Hurler syndrome.
Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Hurler syndrome.
Diet and lifestyle: Dietary modifications or lifestyle adjustments that can prevent or reverse Hurler syndrome have not been reported in the available literature. However, there is some evidence that limiting sugar intake and dairy products has helped reduce the severity of problems associated with excessive mucus production in some individuals. Increased fiber in the diet has also been shown to be helpful in some children with digestive system complications, such as constipation and diarrhea.
Physical therapy and exercise: Physical therapy and daily exercise may delay joint problems and improve the ability to move. However, the developmental problems associated with Hurler syndrome are highly variable and extremely individualized, and excessive extension of affected joints can actually be harmful. Therefore, orthopedic doctors and physical therapists who are experienced with the mobility problems of Hurler syndrome patients should be consulted before any exercise program is undertaken.
Genetic testing: If a blood or tissue sample from a blood relative with Hurler syndrome is available, DNA testing may be utilized to determine if a person is a carrier. Prenatal DNA testing may be performed if there is a family history of Hurler syndrome. However, there are serious risks associated with prenatal testing, including miscarriage. Therefore, patients should discuss the potential health risks and benefits before making any health-related decisions.
Genetic counseling: People with family histories of Hurler syndrome can meet with genetic counselors. These professionals can help patients understand the risks of having a child with Hurler syndrome. A genetic counselor can also explain the different types of genetic tests, including their potential risks and benefits.