Disease

Disease name: Mucopolysaccharidosis, type I

ICD-10 Disease Code: E76.0 Mucopolysaccharidosis, type I

ICD-10 Disease Group: E76- Disorders of glycosaminoglycan metabolism

General description:

Mucopolysaccharidosis type I (MPS I) is a member of a group of rare, genetic disorders that affects several body systems leading to organ damage. The disease arises through mutations in the IDUA gene that encodes an enzyme called alpha-L-iduronidase. The mutated gene results in the cells' inability to produce sufficient levels of the enzyme, or to produce any enzyme at all. Alpha-L-iduronidase is responsible for the breakdown of the carbohydrate glycosaminoglycans (GAGs), which are the by-products of chemical reactions within cells. When cells fail to break down GAGs they accumulate in various tissues in the body and lead to MPS disease symptoms.

Children with MPS are divided into two categories, severe or attenuated, based on the age of disease onset, severity of symptoms, rate of disease progression and early and direct association with the brain. The severity of the disease is directly correlated to the extent of enzyme deficiency. Individuals with MPS I are classified as attenuated or severe. The severe form is known as Hurler syndrome.

Mutations:

The disease is caused by mutations in the IDUA gene which encodes the enzyme alpha-L-iduronidase. The abnormal gene results in complete deficiency of the enzyme in Hurler syndrome or partial function in the attenuated form. As a result of enzyme deficiency, GAGs such as dermatan sulphate and heparan sulphate build up in the lysosomes of cells.

MPS is inherited in a recessive manner meaning that the gene variant in diseased individuals is inherited from both parents.

Disease frequency:

MPS affects male and female populations equally. Prevalence is estimated to be 1/100,000 for Hurler syndrome and 1 in 500,000 for the attenuated type.

Symptoms:

The symptoms of MPS vary depending on several factors including which type of the disease an individual inherits. In severe MPS, skeletal deformities and a delay in motor and intellectual ability are the most prominent symptoms. Symptoms may not be visible at birth and usually manifest at about 6-8 months of age, although symptoms may not become apparent until up to 1 year of age.

Some infants with MPS can have inguinal or umbilical hernias and respiratory tract infections are common in the first year of life. Individuals develop distinctive abnormal facial features such as a thickening of the tongue, lips and skull. Infections to the middle ear are common and can sometimes contribute to hearing impairment. Other symptoms include skeletal disease, clouding of the cornea which can lead to loss of vision, enlargement of organs, and fluid buildup in the brain. Individuals with the severe form of MPS may experience stunted growth and exhibit progressive, debilitation bone and joint disease. Breathing can be difficult for individuals with MPS, who often suffer reduced blood flow throughout the body due to heart valve disease.

Individuals with the attenuated form are of normal height and do not exhibit intellectual disabilities. Otherwise, individuals with attenuated MPS usually experience similar symptoms to the severe form, although symptoms occur much later in life. Typical symptoms include stiff joints, clouding of corneas, carpal-tunnel syndrome, mild skeletal deformities and aortic disease similar to the severe form. Spastic peresis may also occur as a result of compression to the cervical spinal cord.

Treatment:

Treatment of MPS focuses on replacing the missing lysosomal enzyme and alleviating disease symptoms.

The first approach is to replace the missing enzyme through enzyme replacement therapy whereby the enzyme is infused into the patient intravenously. Another method of enzyme replacement can be achieved via haematopoietic stem cell or bone marrow transplantation. The enzyme substitute Laronidase (marketed as Aldurazyme®) was granted EU marketing authorisation (to Genzyme Europe BV) in 2003. Enzyme replacement can greatly improve disease prognosis, but it does not cure MPS.

To treat the specific symptoms of the disease, MPS requires coordination of a multidisciplinary team to target the many varying symptoms of the disease. If the genotype is identified at diagnosis this can also aid in disease treatment.

 

Sources:

Tags

HashtagMucopolysaccharidosis I, MPS I

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