MPS I (Mucopolysaccharidosis Type I, Hurler Syndrome)

Abnormalities in an individual's genetic makeup cause genetic disease.

• MPS I (Hurler syndrome or mucopolysaccharidosis type 1) is a metabolic disorder caused by mutated genes on chromosome 4 that results in deficient lysosomal enzymes. The syndrome usually is diagnosed in young infants (3-6 months of age).
• There are many signs and symptoms of MPS I. The early signs usually are coarsening of facial features with the enlarged mouth, thick lips, and eye problems that progressively become worse.
• Additional signs and symptoms that may develop include:
  • Enlarged head
  • Chronic nasal discharge
  • Retinal degeneration
  • Splenomegaly
  • Enlarged abdominal organs
  • Skeletal dysplasia
  • Joint stiffness
• The cause of MPS I is inherited genetic mutations on chromosome 4 that leads to deficiency in the lysosomal enzyme a-L-iduronidase.
• MPS I is inherited by an autosomal recessive gene that they receive from each parent.
• MPS I is diagnosed by early clinical features of the individual (for example, coarsening of facial features), combined with blood tests and other tests such as spinal X-rays, echocardiography, and other tests as symptoms develop.
• There is no cure for MPS I, and it is difficult to manage (treat). A team approach often is used that includes medical therapy with laronidase (Aldurazyme) and possibly surgery to help reduce some of the symptoms of this inherited disease.
• Life expectancy for a person with MSP I varies according to the severity of the mutations. People with the mildest form (MPS IS) may have a reasonably normal lifespan, those with moderate form (MPS IH/S) may live to teenage or early adulthood, but the most severe form, MPS IH or Hurler syndrome, may allow a lifespan that is rarely longer than 10 years,
• The National MPS Society offers additional support and information about this relatively rare disease.

MSP I (mucopolysaccharidosis type 1) is the most common type of metabolic disorder caused by deficiencies in lysosomal enzymes. Lysosomal enzymes are contained within the lysosomes of cells, organelles that serve to break down many different kinds of substances.

MSP I is caused by mutations in the gene that encodes alpha-L-iduronidase on chromosome 4 that results in deficient lysosomal enzymes that are needed to degrade glycosaminoglycan, a major constituent of connective tissue.

There are many different mutations in this gene. The various mutations cause MPS IH (Hurler syndrome), MPS IS (Scheie syndrome) and MPS IH/S (Hurler/Scheie syndrome), and others.

This article will describe in general MPS I as a single syndrome since MPS IS, MPS IH/S and MPS IH are considered clinical manifestations that range from least severe (MPS IS) to most severe (MPS IH).

As stated previously, the signs and symptoms of MPS may show a spectrum of severity. Some of the signs and symptoms of MPS I are:

• Coarsening of facial features (usually the first abnormality detected at 3-6 months of age)
• Enlarged mouth with thick lips
• Enlarged head
• Chronic nasal discharge
• Progressive corneal clouding
• Retinal degeneration
• Splenomegaly
• Inguinal and umbilical hernias
• Enlarged organs in the abdomen
• Skeletal dysplasia can result in short stature
• Joint stiffness
• Cardiac valve disease, especially of the aortic valve
• Frequent respiratory infections
• Developmental delays with maximum functional age level reaching about 2-4 years

The severest symptoms occur in MPS IH (Hurler syndrome).

The cause of MPS I are genetic mutations on chromosome 4 that lead to a deficiency of the lysosomal enzyme a-L-iduronidase and in turn, leads to mucopolysaccharides accumulating in tissues and organs that interfere with their activity and development.

MPS I is inherited in an autosomal recessive manner. Consequently, nearly all individuals with MPS I receive a recessive gene from each parent. If both of the parents possess the recessive gene, the chances are about 1in 4 that a child will receive an autosomal recessive gene from each parent and develop MPS I.

Pediatricians are usually the first to notice MPS I. Specialists that may be consulted include geneticists, emergency medicine specialists, pulmonologists, neurologists, cardiologists, orthopedists, ophthalmologists, rheumatologists, audiologists, surgeons, child psychologists and genetic counselors.

Clinically, pediatricians may suspect a diagnosis of MPS I if coarsening of facial features are seen at ages of 3-6 months.

Laboratory tests can include the following:

• Examination of lymphocytes in blood smears to look for abnormal cytoplasmic inclusions
• Urinary glycosaminoglycan (gag) measurement
• Measurement of a-l-iduronidase in peripheral blood white cells
• DNA analysis to determine the exact mutation that is present

Other tests may include X-rays of the spine, echocardiography and tests for hearing, vision and developmental milestones. Prenatal diagnosis also may be ordered.

MPS I is treated by a team of doctors (see specialists listed previously) to reduce symptoms, and may include:

• Enzyme replacement therapy with Laronidase can improve walking and pulmonary function in people with MSP I.
• Specialized surgical care can reduce hydrocephalus, and corneal transplantation may help some patients.
• Valve replacement for cardiovascular disease has been accomplished and tracheostomy has been performed to improve breathing in some cases.
• Spinal fusion can help prevent further progression of curvature in the cervical spine, and carpal tunnel release has helped some patients.

The life expectancy is highly variable with MPS I. The life expectancy is related to the severity of the disease. For example, individuals with the mildest form of MPS I (MPS IS) may have a reasonably normal lifespan, while those with intermediate (MPS IH/S) usually live to teen age or early adulthood. Those with severe MPS I (MPS IH or Hurler syndrome) rarely live longer than 10 years.

The national MPS society offers additional information can help find support groups for patients and their families (toll-free number is 877 MPS 1001).