Hurler's syndrome is one of a group of inherited metabolic storage disorders in which the lack of an enzyme affects various organs and tissues, including the brain. Enzymes are proteins that play many roles, including to metabolize (break down) substances in the body. In metabolic storage disorders, the body lacks an enzyme needed to metabolize a substance, such as a sugar. Instead, the substance builds up in the body and causes damage.
An MPS disorder
Hurler's syndrome is also called mucopolysaccharidosis I (MPS-I). It is one of a subgroup of metabolic disorders known as MPS disorders. MPS disorders are caused by a mutation (mistake) in a certain gene. A gene carries an inherited code of instructions that tell the body how to make every cell and substance in the body. The mutated gene in MPS disorders affects an enzyme called alpha-L-iduronidase (IDUA). This enzyme breaks down complex sugars called glycosaminoglycans (GAGs). The body needs GAGs to build bones and tissues, so a healthy body is always making and breaking down GAGs.
In people with MPS disorders, the body keeps making GAGs but does not have the enzyme to break them down. The GAGs are stored in cells throughout the body. As they build up, they damage organs and tissues.
Inheriting Hurler's syndrome
Hurler's syndrome occurs in about one of every 100,000 babies born. A child inherits the syndrome when he or she gets two abnormal genes that affect the IDUA enzyme, one from each parent. If only one parent passes on the gene mutation, the child will not have the disease. Instead, the child will be a "carrier" and may pass the gene mutation to his or her own children.
Signs and symptoms of Hurler's syndrome
As GAGs build up in the body, signs and symptoms of the damage GAGs cause begin to appear. These may include:
Problems with mental function (mental retardation)
Heart problems, including changes in the valves
Hearing problems and frequent ear infections
Large head size, broad forehead and heavy eyebrows
Deformed bones and stiff joints, especially the spine, hips, knees, wrists and fingers
Short size
Breathing problems
Signs and symptoms usually appear within the first year of life and grow worse over time. If the disease is not stopped, children with Hurler's syndrome usually die by 5 to 10 years of age.
Diagnosis
Tests doctors may use to diagnose Hurler's syndrome include:
Urine tests for extra GAGs
Tests of blood and/or skin samples to see if the body is making the IDUA enzyme
Genetic tests for mutations to the gene for the IDUA enzyme
X-rays to check for damage to the spine
Electrocardiogram (EKG) or echocardiogram to check heart function and valve problems
Families affected by Hurler's syndrome may want to talk with a genetic counselor about family planning and the chances of having children with the disorder. Early diagnosis can enable early treatment of a child after birth, which can make a difference in outcomes.
Hurler's syndrome treatments
The goal of treatment for Hurler's syndrome is to give the body the missing enzyme so it can break down GAGs. The two main treatments for children with Hurler's syndrome are enzyme replacement therapy and a bone marrow or cord blood transplant.
Enzyme replacement therapy
For enzyme replacement therapy, a patient is given a drug that has the IDUA enzyme his or her body is missing. The drug is called laronidase, or Aldurazyme. Treatment with laronidase can improve problems with breathing, growth, the bones, joints and heart. However, there is no evidence that it has any effect on mental development problems caused by Hurler's syndrome.
Enzyme replacement therapy may be a good option for children who have a form of MPS I disorder that does not cause mental retardation (Scheie syndrome or Hurler's/Scheie syndrome).
Some children with Hurler's syndrome may be treated with both enzyme therapy and a transplant. This approach is being studied in a clinical trial.
Bone marrow or cord blood transplant
A bone marrow or cord blood transplant (also called a BMT) is the only known treatment that can stop the progression of mental damage caused by Hurler's syndrome.
Transplant for Hurler's syndrome
A transplant replaces the abnormal cells in the bone marrow (the cells with the mutated gene) with healthy cells from a family member or unrelated donor or cord blood unit. The healthy cells provide a source of the enzyme needed to break down GAGs and stop further damage to the body.
In general, a transplant has the best chance of success when it is done soon after diagnosis. Getting a transplant early is important to stop damage caused by the disorder before it becomes severe. Children who receive a transplant early enough can have normal or near-normal mental development. Damage to the organs is stopped and hearing may improve.
However, transplants for children who have already developed severe damage have had disappointing results. If the disorder has caused organ damage, a child has a higher risk of developing life-threatening complications from transplant. In addition, a transplant may not undo damage the disease has already done, especially to the nervous system. However, in some children, there have been improvements in some organs, such as the liver, airway and heart. The child must live with and be treated for the damage that already exists. For example, most children will need multiple surgeries to treat problems with bones, joints and other tissues.
Transplant risks
A transplant is an intense treatment, and some possible side effects can be life-threatening. For children with Hurler's syndrome, three of the most serious risks of transplant are:
Graft-versus-host disease (GVHD) — A common transplant complication that can range from mild to severe. For patients who receive a transplant to treat leukemia, GVHD may be linked with a beneficial graft-versus-leukemia effect. However, there is no benefit to GVHD for patients with Hurler's syndrome.
Graft failure — Graft failure is when the donated cells (the graft) do not grow and make new blood cells for the body (engraft). Graft failure can be life-threatening. If the child's own cells return, he or she may survive, but the progress of the disease will not be stopped. Graft failure is a bigger risk for children being treated for Hurler's syndrome than for many other diseases.
Bleeding in the lungs (pulmonary hemorrhage) — Children with Hurler's syndrome have an increased risk for this serious complication. Bleeding in the lungs can affect how well the child can breathe. In some cases, a child may need a breathing tube and a breathing machine (ventilator).
Learning about Hurler's syndrome and transplant
In the 1980s and 1990s, doctors conducted research studies to learn whether transplant could help children with Hurler's syndrome. Their studies showed that transplant could be life-saving for some children. The studies also showed that some children had normal or near-normal mental development after transplant. Children had a better chance of normal mental development after transplant if they:
Were younger when they received the transplant
Had good mental development at the time of transplant — their mental functions had not yet been severely damaged
It is a good idea to ask your doctor for help interpreting these data and any other survival outcomes data you find. Your doctor can provide context for these data and discuss your specific situation with you. For more things to consider, see Understanding Survival Outcomes Data.
Transplants using family donors
One study included 54 children with Hurler's syndrome who received a transplant from a family member between 1983 and 1995. [1] In this study, at five years:
Of the 28 children who were to receive a transplant from a matched brother or sister, 21 survived (75%). Two patients died during the transplant preparative treatment and did not receive the transplant. The transplant engrafted in all 21 of the children who survived.
Of the 26 children who received a transplant from a partly matched (haploidentical) parent, 14 survived (53%). However, the donor's cells did not engraft in 5 of these 14 children. Instead, the children's own (defective) cells returned and the disease was not stopped.
Transplant stopped damage to mental function for some, but not all, children. Stable mental function was more likely in children who received a transplant before 24 months of age and in children who had better mental function before transplant.
Transplants using unrelated donors
Another study included 40 children who received unrelated donor transplants between 1989 and 1994. [2]
At two years, 20 children were alive (49%).
The donor's cells engrafted in 13 of these children. Five children had their own (defective) cells return, and two had a mixture of donor's cells and their own.
Transplant stopped damage to mental function for some, but not all, children. Stable mental function was more likely in children who received a transplant before 29 months of age and in children who had better mental function before transplant.
Between 1998 and 2006, the National Marrow Donor Program (NMDP) facilitated 30 unrelated donor transplants for children with Hurler's syndrome. The estimated rate of survival at five years was 61% (Figure 1).
Figure 1. Hurler's Syndrome: Survival of pediatric (age < 18) marrow recipients with myeloablative preparative regimens, unrelated donor transplants facilitated by the NMDP, 1998 - 2006. (NMDP data) View Larger VersionHow to read this figure
Cord blood transplants
Recent studies have also shown good results for transplants using cord blood. Cord blood transplants may be an important option for children with Hurler's syndrome, because many do not have a suitable donor in their family and they need to have a transplant quickly. A suitable cord blood unit may be more quickly available than an unrelated adult donor.
One study reported on 20 children treated for Hurler's syndrome with cord blood from unrelated donors between 1995 and 2002. [3]
At the time of the report (333 days to more than seven years after transplant), 17 patients were alive (85%).
The transplant engrafted in all 17 children who survived.
All children had stable or improved mental development after transplant.
The median age of the children at the time of transplant was 16 months, younger than in other studies. The younger age of the children in this study may have contributed to these improved results.
Making treatment decisions
If your child has Hurler's syndrome, it is important to see a doctor who is an expert in this disorder. If your doctor has not treated other patients with Hurler's syndrome, ask him or her to refer you to an expert for consultation. Since Hurler's syndrome gets worse quickly, it is important to see an expert as soon as possible. If transplant is a treatment option for your child, talk with your doctor about the risks, limits and possible benefits of transplant.
More information on Hurler's syndrome
You can get further information about Hurler's syndrome from disease-specific organizations, such as the National MPS Society: http://www.mpssociety.org.
Peters C, Shapiro EG, Anderson J, et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group. Blood. 1998; 91(7):2601-2608. http://www.bloodjournal.org/cgi/content/abstract/91/7/2601
Paul Orchard, M.D., University of Minnesota BMT Program at Fairview University Medical Center, Minneapolis, Minn. Charles Peters, M.D., Children's Mercy Hospital, Kansas City, Mo.
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