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.
Forms of the disorder
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 have 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 1 in every 100,000
births and the frequency of Scheie syndrome is estimated at 1 in every 500,000
births.
Clinical features
Individuals with Hurler syndrome usually begin to display symptoms by 1 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.
Genetics of the disorder
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. More here
about autosomal recessive inheritance.
Treatment
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.
Registry
The MPS I Registry is an ongoing, strictly observational study that records
the natural history and outcomes of patients with MPS I. There is no
experimental intervention involved. The purpose of this registry is to collect
clinical information on a large number of patients throughout the course of
their lives. The registry is a way for healthcare professionals to share
information in a manner that respects patient confidentiality, but at the same
time contributes to a greater understanding of the disorder and serves as a tool
in the ongoing search for a cure for MPS I.