Mucopolysaccharidosis & Mucolipidosis

Mucopolysaccharidoses (MPS) are a group of genetic disorders each of which is caused by the deficiency of an enzyme (a protein that produces chemical reactions in the body) that breaks down one or more types of mucopolysaccharides, also referred to as glycosaminoglycans (GAGs). GAGs are long, repeating chains of complex sugar molecules that are normal chemical components of bones, cartilage and many other tissues within the body. They are constantly being “turned over,” meaning that new GAGs are produced as others are broken down. If the GAGs cannot be broken down normally, they accumulate in excess in various tissues of the body resulting in the clinical features associated with an MPS disorder.

Changes in specific genes result in the deficiency or absence of the enzyme. The MPS disorders are categorized into several groups based on the clinical features and specific enzyme deficiency. An individual is usually suspected of having an MPS disorder after developing characteristic physical findings. The diagnosis is further confirmed by laboratory testing. Clinical features of these conditions may vary depending on the specific diagnosis.

Mucopolysaccharidosis I (MPS I)

MPS I is caused by a deficiency of an enzyme (alpha-L-iduronidase) that is needed to break down the mucopolysaccharides/glycosaminoglycans (GAGs) called dermatan and heparan sulfate, which are found in the central nervous system and throughout other systems of the body. GAGs are long, repeating chains of complex sugar molecules. When the enzyme is absent, a progressive buildup of the GAG material occurs in many of the tissues of the body and leads to many health problems.

What Causes MPS?

MPS I is inherited as an autosomal recessive trait. Here's how that works: All individuals have two copies of the specific MPS I gene and usually both function normally. However, children with MPS I have alterations in both copies of their genes so that neither gene copy works properly. Children receive one copy of the altered gene from their mother and one copy of the altered gene from their father. The parents are not affected with the condition because they have one normal copy of the gene paired with one altered copy of the gene. The normal gene produces enough of the specific enzyme to prevent the disorder. This is referred to as being a carrier for the condition. When both parents are carriers, they have a 25% chance with each pregnancy to have an affected child. In turn, parents who are carriers have a 75% chance with each pregnancy to have an unaffected child. Learn about autosomal recessive inheritance.

What Are the Symptoms of MPS?

Individuals with Hurler syndrome usually begin to display symptoms by one year of age. These symptoms may include kyphosis (curvature of the spine causing a “lump on the back”), joint stiffness, coarse facial features (flattened nose bridge, thick lips and an enlarged tongue), corneal clouding, hearing loss, heart problems, an enlarged liver and spleen, hernias, chronic nasal congestion and ear infections.

Developmental delay may become apparent within the first two years of life and progress as the child ages.

Individuals with Scheie syndrome generally have normal intelligence and typically live well into adulthood. However, they may present with a variety of physical problems. These may include joint stiffness, heart problems, corneal clouding and hearing loss.

Individuals with Hurler/Scheie syndrome usually have variable clinical symptoms of intermediate severity between the mildest and most severe forms of MPS I.

How Is MPS Diagnosed?

MPS I is a variable disorder and is traditionally divided into three possible forms. The more severe form is called Hurler syndrome (MPS IH). A wide range of milder forms has been observed. These forms are referred to as attenuated MPS I. Patients at the mildest end of the attenuated range are referred to as having Scheie syndrome (MPS IS) while those with problems in between those observed in Hurler and Scheie syndromes are referred to as having Hurler-Scheie syndrome (MPS IH/S). The frequency of Hurler syndrome is estimated as one in every 100,000 births, and the frequency of Scheie syndrome is estimated at one in every 500,000 births.

How Is MPS Treated?

Despite the fact that there is no cure for MPS I, several therapies do exist to treat the symptoms of the disorder. Possible therapies include stem cell transplantation and enzyme replacement therapy (ERT). Management of the disorder also involves symptomatic treatment of specific complications that can arise.

Mucopolysaccharidosis & Mucolipidosis