Science & Technology in Action

4th Edition

The Treatment of Hurler Syndrome

Genzyme

Hurler syndrome, also known as MPS-I, is a genetic disease whose effects on an individual are varied and severe. It is caused by an error in the production of a single enzyme.
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Contains the full lesson along with a supporting toolkit, including teachers’ notes.

Lesson excerpt

Hurler syndrome is the most severe form ofmucopolysaccharidosis type I (MPS I) and takes its name from Gertrude Hurler, the general practitioner who described children with the condition in 1919. At the time little was known about its cause. In 1962, Dr. Scheie reported patients with corneal clouding and other effects that came to be known as Scheie syndrome. In 1971 it was discovered that Scheie and Hurler syndromes were due to the sameenzyme deficiency. Later in the 1970s intermediate conditions were described as Hurler-Scheie syndrome; it now seems that all three conditions are part of a wide spectrum of effects of a defect in the gene that codes for the production of the enzyme alpha-Liduronidase. The body produces a variety of important substances calledglycosaminoglycans (GAGs) – formerly known as mucopolysaccharides. They are composed of sugar and amino acid sub-units; examples include dermatan sulfate and heparin. In the absence of alpha-L-iduronidase GAGs accumulate in tissues and cause numerous problems.

Symptoms
The symptoms of the disease include any or all of the following: dwarfism, hunchback, coarse gargoyle-like facial features, mental retardation, corneal clouding, deafness, chronic runny nose,hernia, heart problems, enlarged tongue, hyperactivity, depression, painful and stiff joints, as well as a dramatically shortened life span; sufferers rarely live beyond 10 or 15 years of age. The symptoms are wide-ranging and severe because every tissue in the body is affected.

Diagnosis
It is a rare disease with an incidence of around 1:100,000 for both sexes. The equal frequency in both sexes indicates that it is notsex-linked. An affected child may appear normal until about one year old, but then the head may appear to become abnormally large or colds and ear infections may become frequent. As time progresses, the other symptoms become more obvious.

Excretion of mucopolysaccharides such as heparin sulfate B and condroitin in the patient’s urine is one of the easiest ways to diagnose the condition but blood enzyme level tests are perhaps the most certain method. genetic screening is also used to test for mutations in the gene, but this is usually used as a confirmatory test. A number of techniques can be used forprenatal diagnosis of MPS I.

Quiz questions

  1. Hurler-Schie syndrome is the most severe form of mucopolysaccharidosis false
  2. Mucopolysaccharides are glycosaminoglycans. true
  3. MPS I has a spectrum of symptoms that range in severity, not all suffers exhibit the same symptoms. true
  4. MPS I disease has a higher incidence in males false
  5. Urine tests to determine enzyme concentrations are the most certain way to diagnose MPS I. false
  6. As MPS I is recessive, if parents are both carriers their child is certain to have MPS I disease.
  7. In a healthy person alpha-L-iduronidase breaks down GAGs in the lysosome. true
  8. None of the available treatments provide a solution to reverse the neurological damage of the disease. true