Pathology

Causes and Symptoms of Hurler Syndrome



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Hurler’s disease is one of over 40 different lysosomal storage diseases. These diseases are the result of mutated genes that affect the hydrolytic enzymes found in the lysosomes of cells. This organelle is responsible for the digestion of cellular waste. Malfunctioning or deficient enzymes mean that some of the waste is not disposed of and builds up within the cell, often with severe consequences. As with many other lysosomal storage diseases, it primarily affects children and often at a very young age.

This disease was named for German paediatrician Gertrud Hurler, who first described it in 1919. It is classified as one of the mucopolysaccharidosis lysosomal storage diseases. It is also known as MPS 1. In the case of Hurler’s disease, the enzyme that is not produced is alpha-L-iduronidase (IDUA). This is one of the enzymes responsible for breaking down glycosaminoglycans (GAGs) in the cell.

GAGs are involved in the production of bone and tissue and are in a constant state of production, usage and disposal in the healthy body. In children with Hurler’s, GAGs build up in excessive amounts causing organ and tissue damage. The side effects of this build-up often become apparent within the first year of life. Left untreated, and sometimes even with treatment, most affected children will die between the ages of five and ten years. Cause of death is usually organ failure.

Lysosomal storage diseases are genetic diseases, caused by mutated genes inherited from both parents. Hurler’s occurs in 1 in 100,000 children. If someone in the family is diagnosed with Hurler’s disease the whole family should be tested for presence of the gene. Although other individuals may not be affected, they may be carriers of the gene (ie they inherited a gene from one parent but not the other) and can pass it on to their own offspring.

Common problems presenting in affected people include heart and valve issues, hearing problems and increased number of ear infections, respiratory difficulties, short stature, deformities of the bones and stiffness of the joints (particularly wrists, fingers, knees, hips and spine), disproportionate head size, low brow with broad forehead, and decreased mental function, which worsens as the disease progresses. The progression of the illness can be quite rapid.

There is a range of severity. The most severely affected patients are referred to as having Hurler’s disease while the least affected are considered to have Scheie’s syndrome. Those in between the two extremes are often described as having Hurler Scheie syndrome. At the mild end, Scheie’s syndrome sufferers may have no mental function disabilities or very mild ones and may, with treatment, live a relatively normal life span.

There are several different tests for Hurler`s disease. Urine tests for excess GAGs, enzyme assays using blood and skin samples and gene testing for mutations of the gene responsible for IDUA enzyme function are the most common ones. Electrocardiograms to check heart function and x-rays of the spine may also be performed.

There is no cure for any of the lysosomal storage diseases and Hurler’s is no exception. Symptoms and organ issues are usually addressed by an array of specialists under the direction of a doctor specializing in genetic diseases. There are two treatments in use that attempt to tackle the enzyme deficiency itself – enzyme replacement therapy (ERT) and bone marrow transplants (BMT).

Enzyme replacement therapy uses Laronidase or Aldurazyme to take the place of the missing enzyme. This treatment can help arrest some of the physical consequences of Hurler’s disease. It has no affect on mental function deterioration though. It is a good option for children with Scheie’s syndrome who have no central nervous system problems. There are studies currently underway that are examining combing ERT with BMT as a treatment option for more severely affected children.

Bone marrow transplants use the healthy cells from a family member or anonymous donor or cord blood donor to replace the damaged cells in the patient. The goal is to have the healthy cells take over the digestion of GAGs, stopping the progression of the disease. This works best if performed as soon as possible after diagnosis. The more severe the damage, the less likely it is to be successful. This is particularly true with respect to arresting mental deterioration. Transplants are risky operations and patients with severely damaged organs may not be good surgical candidates. If done soon enough some of the damage to the liver, heart and lungs may actually be reversed.

There are three main risks to transplants beyond the surgery itself. Graft versus host disease (GVHD) is a risk to all transplants patients. The recipient may reject the new cells entirely or develop some adaptational difficulties related to the new cells. Graft failure occurs when the healthy cells that have been transplanted fail to thrive in their new environment. This can be life-threatening. If the child’s own cells return to production the child may survive but the disease will continue to progress. The final risk is particularly common in individual’s with Hurler’s disease. Pulmonary hemorrhage occurs more often in these children due to lung damage from GAG buildup. This may result in the patient needing a breathing tube and ventilator to breathe.

There are a lot of risks to doing a transplant but it may also save the child’s life, particularly if performed early enough in the disease’s progression. For the more mildly affected patients with Scheie’s syndrome, ERT may be enough to allow them to live out a normal lifespan. In all cases, multiple surgeries to correct and handle organ damage that has already occurred is to be expected. Because lysosomal storage diseases are so rare, there is less funding towards finding treatments and cures for them. At this time the best options remain early diagnosis, ERT and BMT. 

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ARTICLE SOURCES AND CITATIONS
  • InfoBoxCallToAction ActionArrowhttp://marrow.org/Patient/Disease_and_Treatment/About_Your_Disease/Metabolic_Disorders/Hurler_s_Syndrome.aspx
  • InfoBoxCallToAction ActionArrowhttp://www.medschool.ucsf.edu/lysosomal/hurler/
  • InfoBoxCallToAction ActionArrowhttp://marrow.org/Patient/Disease_and_Treatment/About_Your_Disease/Metabolic_Disorders/Hurler_s_Syndrome.aspx
  • InfoBoxCallToAction ActionArrowhttp://marrow.org/Patient/Disease_and_Treatment/About_Your_Disease/Metabolic_Disorders/Hurler_s_Syndrome.aspx