CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0401/04013.txt

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$Unique_ID{BRK04013}
$Pretitle{}
$Title{Mucopolysaccharidosis}
$Subject{Mucopolysaccharidosis MPS MPS Disorder MPS I H (Hurler Disease) MPS I
S (Scheie Syndrome) MPS I H/S (Hurler/Scheie Syndrome) MPS II-XR, severe
(Hunter Syndrome) MPS II-XR, mild (Hunter Syndrome) MPS II-AR, autosomal
(Hunter Syndrome) MPS III A, B, C, and D (Sanfilippo A) MPS IV A and B
(Morquio A) MPS V (No longer used) MPS VI, severe, intermediate, mild
(Maroteaux-Lamy) MPS VII (Sly Syndrome) MPS VIII (No longer used)
Pseudo-Hurler Polydystrophy Ganglioside Sialidase Deficiency I-Cell Disease }
$Volume{}
$Log{}

Copyright (C) 1989 National Organization for Rare Disorders, Inc.

688:
Mucopolysaccharidosis


** IMPORTANT **
It is possible that the main title of the article (Mucopolysaccharidosis)
is not the name you expected.  Please check the SYNONYM listing to find the
alternate names and disorder subdivisions covered by this article.

Synonyms

     MPS
     MPS Disorder

Disorder Subdivisions:

     MPS I H (Hurler Disease)
     MPS I S (Scheie Syndrome)
     MPS I H/S (Hurler/Scheie Syndrome)
     MPS II-XR, severe (Hunter Syndrome)
     MPS II-XR, mild (Hunter Syndrome)
     MPS II-AR, autosomal (Hunter Syndrome)
     MPS III A, B, C, and D (Sanfilippo A)
     MPS IV A and B (Morquio A)
     MPS V (No longer used)
     MPS VI, severe, intermediate, mild (Maroteaux-Lamy)
     MPS VII (Sly Syndrome)
     MPS VIII (No longer used)

Information on the following diseases can be found in the Related
Disorders section of this report:

     Pseudo-Hurler Polydystrophy
     Ganglioside Sialidase Deficiency
     I-Cell Disease

General Discussion

** REMINDER **
The information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.

The Mucopolysaccharidoses are a group of hereditary diseases of lysosomal
storage.  They are characterized by deposits of mucopolysaccharides in the
arteries, skeleton, eyes, joints, ears, skin and teeth.  These deposits may
also be found in the respiratory system, liver, spleen, central nervous
system, blood cells and bone marrow.

Symptoms

MPS consists of a group of hereditary diseases.  These diseases are
characterized by an abnormal accumulation of mucopolysaccharides, especially
in the cartilage and bone tissue.  In general these disorders are progressive
and usually disabling.  The child may appear normal at birth and around the
age of one begin to show signs of both growth and mental retardation.  After
the age of three or four growth may seem to cease.  This growth retardation
occurs in all of the MPS disorders except the Scheie Syndrome.  Many patients
develop serious vision and hearing problems.  Stiff joints occur in all but
the Morquio Syndrome.  Excessive hairiness (hirsutism), dwarfism, and heart
problems (especially Angina Pectoris) are common features of most of the
syndromes.  Breathing problems may occur as a result of the narrowing of the
airways due to skeletal deformities.  The liver and spleen are enlarged in
most MPS patients.  The central nervous system and brain may also be
affected.

Disorder Subdivisions:

Mucopolysaccharidoses I in the severe form is Hurler Syndrome.  It is
characterized by high concentrations of dermatan and heparan sulfates, in the
urine.  Symptoms of the disorder first become evident at six months to two
years of age.  There is developmental delay, recurrent urinary and upper
respiratory tract infections, noisy breathing and a persistent nasal
discharge.  Swelling of the head (hydrocephalus) is common after the age of
two.  Other physical problems may include clouding of the cornea of the eye,
an unusually large tongue, misaligned teeth, severe deformity of the spine,
joint stiffness and clawlike hands.  Mental development begins to regress at
about the age of two.  (For more information on this disorder choose "Hurler"
as your search term in the Rare Disease Database.)

Scheie Syndrome is the milder form of MPS I.  The patient has a normal
intelligence, stature and life expectancy, but suffers from physical symptoms
such as stiff joints, clouding of the cornea, and the backward flow of blood
into the heart (aortic regurgitation).  The onset of symptoms in patients
with Scheie Syndrome usually occurs after the age of five years.  However,
diagnosis is commonly delayed to between ten to twenty years of age.  (For
more information on this disorder choose "Hurler" as your search term in the
Rare Disease Database.)

Hurler-Scheie Syndrome is an intermediate form of MPS I and is
characterized by normal intelligence but progressive physical involvement
which is milder than Hurler Syndrome.  Corneal clouding, joint stiffness,
deafness and valvular heart disease can develop by the early to mid-teens,
causing significant impairment.  (For more information on this disorder
choose "Hurler" as your search term in the Rare Disease Database.)

Mucopolysaccharidoses II, Hunter Syndrome, is the most prevalent form of
MPS.  In the severe form, physical and mental development reach a peak at two
to four years with subsequent deterioration.  Recurrent urinary and upper
respiratory tract infections, a chronic runny nose, liver and spleen
enlargement, joint stiffness and growth failure commonly occur.  There is
coarsening of the facial features with thickening of the nostrils, lips and
tongue.  Swelling of the head (hydrocephalus) is commonly found in this form
of Hunter Syndrome as is thicker than normal skin, short neck, widely spaced
teeth, and hearing loss of varying degree.  Skin lesions on the arm or the
posterior chest wall, extra-high arched feet and diarrhea may also occur.
(For more information on this disorder choose "Hunter" as your search term in
the Rare Disease Database.)

The milder form of Hunter MPS II is characterized by less severe physical
deterioration and normal intelligence.  Complications of the mild form of the
disorder may include heart disease, hearing impairment, reduced circulation
and joint stiffness in the hands.  (For more information on this disorder
choose "Hunter" as your search term in the Rare Disease.)

The autosomal form of Hunter MPS II can have a combination of the
symptoms of both the severe and mild forms of Hunter Syndrome.  (Choose
"Hunter" as your search term on the Rare Disease Database.)

Mucopolysaccharidosis III is titled Sanfilippo Syndrome and is
characterized by progressive mental retardation and the excretion of heparan
sulfate in the urine.  There is variability in the degree of mental
retardation.  The patient will usually begin to show hyperactivity and sleep
disorders around the age of two or three.  The child may be able to start
school but will usually become a "behavior problem" and loose the ability to
speak.

The excretion of heparan sulfate is the strongest evidence of MPS III.
MPS III A, B, C, and D range in severity from A the most severe to D the
least severe.  The means of classification of the various types of MPS III
rests in the lack of specific enzymes in the process of eliminating heparan
sulfate.

Type A lacks the enzyme heparan N-sulfatase.
Type B lacks the enzyme acetylated glucosamines initially present in
heparan sulfate.
Type C lacks the enzyme N-acetyltransferase reaction.
Type D lacks the enzyme sulfatase reaction.

(For more information on this disorder choose "Sanfilippo" as you search
term in the Rare Disease Database.)

Mucopolysaccharidosis IV is characterized by the excretion of keratan
sulfate in the urine.  This syndrome is also known as the Morquio Syndrome.
The developmental abnormalities may be detected as early an eighteen months
to two years of age.  The skeletal abnormalities are milder in Morquio B than
in Morquio A.  These may include an enlarged head, a broad mouth, prominent
cheekbones, an unusually small nose, widely spaced and thinly enameled teeth,
and widely separated eyes with corneal clouding.  Later, patients tend to
develop abnormally short necks, short barrel chests, disproportionately long
arms, enlarged and possibly hyperextensible wrists, stubby hands and "knock
knees".  Together with the misaligned knees and knobby joints, the child may
be "pigeon-toed", causing a wobbly gait.  There may also be enlargement of
the liver, curvature of the spine, heart problems and hearing loss.  The
intelligence of the patient is usually normal.  (For more information on this
disorder choose "Morquio" as your search term in the Rare Disease Database.)

Mucopolysaccharidosis V, (The Scheie Syndrome) is now designated as MPS I
because of the close relationship to the Hurler syndrome.  (Choose "Hurler"
as your search term in the Rare Disease Database.)

Mucopolysaccharidosis VI, also known as Maroteaux-Lamy Syndrome, is
classified by severe, mild and intermediate types.  It is characterized by
growth retardation beginning around two to three years of age.  There is a
coarsening of facial features and abnormalities in the bones of hands and
spine creating a dwarflike appearance.  Stiff joints, a hunched spine,
prominent chestbone, and pain in the hip bone all tend to appear after the
first four years.  There may also be noisy and strained breathing,
intermittent deafness and an enlarged liver and spleen.  (For more
information on this disorder choose "Maroteaux" as your search term in the
Rare Disease Database.)

Mucopolysaccharidosis VII is also called Sly Syndrome.  It is
characterized by an increased amount of dermatan sulfate and heparan sulfate
in the urine.  Sly Syndrome usually results in mental retardation.  Other
symptoms may include short stature and skeletal abnormalities such as joint
contractures, dislocated hips, and spinal malformations.  The liver and
spleen may be enlarged, there may be hernias in the groin and navel areas and
there may also be clouding of the cornea of the eye.  This type of
Mucopolysaccharidoses VII is very rare and affects less than twenty persons
worldwide.  (For more information on this disorder choose "Sly" as your
search term in the Rare Disease Database.)

Mucopolysaccharidoses VIII, DiFerrante Syndrome is not a valid disorder,
and it is no longer used.

Causes

All of the MPS diseases result from deficiency of specific lysosomal enzymes
involved in the breaking down of dermatan sulfate, heparan sulfate, or
keratan sulfate, either alone or together.  These mucopolysaccharides
accumulate in tissues and organs and are also excreted in the urine.  All of
these diseases are inherited as autosomal recessive except for the Hunter
Syndrome which is X-linked recessive.

Human traits, including the classic genetic diseases, are the product of
the interaction of two genes, one received from the father and one from the
mother.  In recessive disorders, the condition does not appear unless a
person inherits the same defective gene for the same trait from each parent.
If one receives one normal gene and one gene for the disease, the person will
be a carrier for the disease, but usually will show no symptoms.  The risk of
transmitting the disease to the children of a couple, both of whom are
carriers for a recessive disorder, is twenty-five percent.  Fifty percent of
their children will be carriers, but healthy as described above.  Twenty-five
percent of their children will receive both normal genes, one from each
parent, and will be genetically normal.

X-linked recessive disorders are conditions which are coded on the X
chromosome.  Females have two X chromosomes, but males have one X chromosome
and one Y chromosome.  Therefore, in females, disease traits on the X
chromosome can be masked by the normal gene on the other X chromosome.  Since
males only have one X chromosome, if they inherit a gene for a disease
present on the X, it will be expressed.  Men with X-linked disorders transmit
the gene to all their daughters, who are carriers, but never to their sons.
Women who are carriers of an X-linked disorder have a fifty percent risk of
transmitting the carrier condition to their daughters, and a fifty percent
risk of transmitting the disease to their sons.

Affected Population

All of the MPS disorders affect males and females in equal numbers with the
exception of the Hunter Syndrome which affects only males.

Related Disorders

Symptoms of the following disorders can be similar to those of MPS.
Comparisons may be useful for a differential diagnosis:

Pseudo-Hurler Polydystrophy is an autosomal recessive inherited disorder,
characterized by onset in childhood, painless joint stiffness, decreased
mobility, short stature, some coarseness of the facial features, mild mental
retardation, evidence of multiple defective bone formations and aortic valve
(heart) disease.  (For more information on this disorder, choose "Pseudo-
Hurler" as your search term in the Rare Disease Database).

Ganglioside Sialidase Deficiency is characterized by a deficiency in the
enzyme ganglioside sialidase which causes abnormalities of connective tissue
cells, defects of the cornea and retardation of physical and mental
development.  The first symptom usually is clouding of the eye's cornea.  The
development of physical and mental retardation usually begins after the
child's first year of life.  (For more information on this disorder, choose
"Ganglioside" as your search term in the Rare Disease Database).

I-Cell Disease begins very early in life.  By the age of six months
children have begun to show symptoms such as coarse facial features (e.g., as
depressed nasal bridge), a long and narrow head, excessive hair growth, and a
low forehead.  They may also show severe skeletal changes including curvature
of the spine, a lumbar hump, problems with their vertebra, widening of the
ribs, and pointing of the long bones of the hands.  Mental and physical
retardation is common.  Frequent respiratory infections and severe joint
contractures occur as do opacities of the cornea of the eye.  (For more
information on this disorder, choose "I-Cell" as your search term in the Rare
Disease Database).

Therapies:  Standard

Treatment of all of the Mucopolysaccharidoses disorders is symptomatic and
supportive.  If hernias, joint contractures, hydrocephalus and eye problems
occur, surgery to correct the problem may be indicated.  Physical therapy may
also be of benefit.

Genetic counseling will be of benefit to families of patients with MPS
disorders.

Therapies:  Investigational

Since prenatal diagnosis is possible through the use of amniocentesis and
tissue sampling of the embryo, new diagnostic interventions are being
developed.  Experimental treatments scientists are trying to develop include
replacing defective enzymes via enzyme replacement therapy and/or bone marrow
transplants.  Scientific study of gene replacement in animal models raises
the hope that gene replacement therapy may someday be made available to
people with serious genetic disorders.

This disease entry is based upon medical information available through
August 1989.  Since NORD's resources are limited, it is not possible to keep
every entry in the Rare Disease Database completely current and accurate.
Please check with the agencies listed in the Resources section for the most
current information about this disorder.

Resources

For more information on Mucopolysaccharidoses, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     MPS (Mucopolysaccharidoses) Research Funding Center, Inc.
     1215 Maxfield Road
     Hartland, MI 48029
     [phone]

     National MPS Society
     17 Kramer Street
     Hicksville, NY 11801
     [phone]

     Society of MPS Diseases
     30 Westwood Drive
     Little Chalfont, Bucks, England

     Society of Mucopolysaccharide Diseases, Inc.
     382 Parkway Blvd.
     Flin Flon, Manitoba, Canada R8A OK4

     National Digestive Diseases Information Clearinghouse
     Box NDDIC
     Bethesda, MD  20892
     [phone]

For genetic information and genetic counseling referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.:  Charles R. Scriver, et
al., eds.; McGraw Hill, 1989.  Pp. 1565-1588.

THE MUCOPOLYSACCHARIDOSES AND ANAESTHESIA:  A REPORT OF CLINICAL
EXPERIENCE.  I.A. Herrick, et al.; Can J Anaesth (January, 1988, issue 35
(1)).  Pp. 67-73.

MUCOPOLYSACCHARIDOSES AND ANAESTHETIC RISKS.  P. Sjogren, et al.; Acta
Anaesthesiol Scand (April, 1987, issue 31 (3) ).  Pp. 214-218.

ELECTRORETINOGRAPHIC FINDINGS IN THE MUCOPOLYSACCHARIDOSES.  R.C. Caruso,
et al.; Ophthalmology (December, 1986, issue 93 (12)).  Pp. 1612-1616.