What are the different types of the
mucopolysaccharidoses?
Seven distinct clinical types and numerous subtypes of the mucopolysaccharidoses
have been identified. Although each mucopolysaccharidosis (MPS) differs clinically,
most patients generally experience a period of normal development followed by a
decline in physical and/or mental function.
MPS I has historically been divided into three broad groups based on severity of
symptoms--Hurler, Hurler-Scheie, and Scheie (in decreasing order of severity). It is
now more appropriate to view MPS I as a continuous spectrum of disease, with the
most severely affected individuals on one, the less severely affected (attenuated) on the
other end, and a wide range of different severities in between. All individuals with MPS
I have an absence of, or insufficient levels of, the enzyme alpha-L-iduronidase. Children
with MPS I inherit a defective gene from both their mother and father.
In the more severe form of MPS I, developmental delay is evident by the end of the
first year, and patients usually stop developing between ages 2 and 4. This is
followed by progressive mental decline and loss of physical skills. Language may be
limited due to hearing loss and an enlarged tongue. In time, the clear layers of the
cornea become clouded and retinas may begin to degenerate. Carpal tunnel
syndrome (or similar compression of nerves elsewhere in the body) and restricted
joint movement are common.
Affected children may be quite large at birth and appear normal but may have inguinal
(in the groin) or umbilical (where the umbilical cord passes through the abdomen)
hernias. Growth in height may be faster than normal but begins to slow before the end
of the first year and often ends around age 3. Many children develop a short body trunk
and a maximum stature of less than 4 feet. Distinct facial features (including flat face,
depressed nasal bridge, and bulging forehead) become more evident in the second
year. By age 2, the ribs have widened and are oar-shaped. The liver, spleen, and heart
are often enlarged. Children may experience noisy breathing and recurring upper
respiratory tract and ear infections. Feeding may be difficult for some children, and
many experience periodic bowel problems. Children with severe MPS I often die before
age 10 from obstructive airway disease, respiratory infections, or cardiac complications.
Although symptoms generally begin to appear after age 5 in children with attenuated
MPS I, the diagnosis is most commonly made after age 10. Children with attenuated
MPS I have normal intelligence or may have mild learning disabilities; some may
have psychiatric problems. Glaucoma, retinal degeneration, and clouded corneas
may significantly impair vision. Other problems include carpal tunnel syndrome or
other nerve compression, stiff joints, claw hands and deformed feet, a short neck,
and aortic valve disease. Some affected individuals also have obstructive airway
disease and sleep apnea. Persons with attenuated MPS I can live into adulthood.
Within the MPS I disease spectrum are children whose symptoms generally begin
between ages 3 and 8. Children may have moderate mental impairment and learning
difficulties. Skeletal and systemic irregularities include short stature, marked
smallness in the jaws, progressive joint stiffness, compressed spinal cord, clouded
corneas, hearing loss, heart disease, coarse facial features, and umbilical hernia.
Respiratory problems, sleep apnea, and heart disease may develop in adolescence.
Some persons need continuous positive airway pressure during sleep to ease
breathing. Life expectancy is generally into the late teens or early twenties.
Although no studies have been done to determine the frequency of MPS I in the United
States, studies in British Columbia estimate that one in 100,000 babies born has severe
MPS I. The estimate for attenuated MPS I is one in 500,000 births and one in 115,000
births for individuals whose disease symptoms fall between severe and attenuated.
MPS II, Hunter syndrome, is caused by lack of the enzyme iduronate sulfatase.
Although it was once divided into two groups based on the severity of symptoms, MPS
II is now considered a continuous spectrum of disease. MPS II is the only one of the
mucopolysaccharidoses in which the mother alone can pass the defective gene to a
son. The incidence of MPS II syndrome is estimated to be one in every 100,000 to
150,000 male births.
Children with the more severe form of MPS II share many of the same clinical
features associated with severe MPS I but with milder symptoms. Onset of the
disease is usually between ages 2 and 4. Developmental decline is usually noticed
between the ages of 18 and 36 months, followed by progressive loss of skills. Other
clinical features include coarse facial features, skeletal irregularities, obstructive
airway and respiratory complications, short stature, joint stiffness, retinal
degeneration (but no corneal clouding), communicating hydrocephalus (see "What
are the signs and symptoms?"), chronic diarrhea, enlarged liver and spleen, and
progressive hearing loss. Whitish skin lesions may be found on the upper arms,
back, and upper legs. Death from upper airway disease or cardiovascular failure
usually occurs by age 15.
Physical characteristics of children with a less severe form of MPS II are less obvious
and progress at a much slower rate. Diagnosis is often made in the second decade
of life. Intellect and social development are not affected. Skeletal problems may be
less severe, but carpal tunnel syndrome and joint stiffness can restrict movement and
height is somewhat less than normal. Other clinical symptoms include hearing loss,
poor peripheral vision, diarrhea, and sleep apnea, although respiratory and cardiac
complications can contribute to premature death. Persons with attenuated MPS II
may live into their 50s or beyond.
