CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0422/04225.txt

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$Unique_ID{BRK04225}
$Pretitle{}
$Title{Sly Syndrome}
$Subject{Sly Syndrome Mucopolysaccharidosis VII MPS VII Beta-Glucuronidase
Deficiency MPS Disorder }
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Copyright (C) 1986, 1987, 1988, 1990 National Organization for Rare
Disorders, Inc.

291:
Sly Syndrome

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

Synonyms

     Mucopolysaccharidosis VII
     MPS VII
     Beta-Glucuronidase Deficiency
     MPS Disorder

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.


Mucopolysaccharidoses (MPS Disorders) are a group of rare genetic
disorders caused by the deficiency of one of ten specific lysosomal enzymes,
resulting in an inability to metabolize complex carbohydrates
(mucopolysaccharides) into simpler molecules.  The accumulation of these
large, undegraded mucopolysaccharides in the cells of the body causes a
number of physical symptoms and abnormalities.

Sly syndrome is characterized by a deficiency in the enzyme
beta-glucuronidase, which leads to an excess of dermatan sulfate in the urine.
Patients with this syndrome are similar to patients with MPS I with a wide
range of clinical involvement from mild to severe.  Mental retardation
commonly occurs with short stature, skeletal, intestinal and corneal
abnormalities.

Symptoms

Sly Syndrome is characterized by an increased amount of dermatan sulfate and
heparan sulfate in the urine.  Patients with this syndrome are often mentally
retarded.  Other symptoms may include a short stature, and skeletal
abnormalities, such as joint contractures, dislocated hips, and spinal
malformations.  An enlarged liver and spleen (hepatosplenomegaly), and
clouding of the eye's cornea may be seen in this syndrome.  Hernias in the
groin and navel (umbilical) areas may also occur.  Blood from the aorta may
flow back into the left ventricle of the heart (aortic regurgitation).

Causes

Sly Syndrome is an autosomal recessively inherited disorder, in which the
enzyme beta-glucuronidase is deficient, which causes the symptoms of this
disorder.  (Human traits including the classic genetic diseases, are the
product of the interaction of two genes for that condition, 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 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.)

Affected Population

Sly Syndrome affects males and females equally.  It is an extremely rare
disorder with less than 20 patients reported throughout the world.

Related Disorders

DiFerrante syndrome (Mucopolysaccharidosis VIII) is a disorder described in a
single patient with clinical and biochemical features of Morquio and
Sanfilippo syndromes.  The disorder had been reported to be due to a
deficiency of glucosamine-6-sulfate sulfatase.  Subsequently, this disorder
was called MPS VIII (DiFerrante syndrome).  Dr. DiFerrante later found that
the enzyme was normal in his patient, and the disorder had been misdiagnosed.
Therefore, DiFerrante syndrome is not a valid medical disorder.

The Mucolipidoses (ML Disorder) are a family of similar disorders,
producing symptoms very much like those of the Mucopolysaccharidoses (MPS).
(For more information, choose "ML Disorder" as your search term in the Rare
Disease Database.)

I-cell disease, or Mucolipidosis Type II, resembles Hurler syndrome and
the two disorders are very difficult to distinguish.  I-cell disease has
similar physical and mental deterioration as MPS I, but usually occurs
earlier and is more severe.  I-cell disease is characterized by diffused
deficiency of lysosomal enzymes within the cell and is not associated with
excretion of mucopolysaccharides in the urine.

Pseudo-Hurler Dystrophy (ML III) is also transmitted by autosomal
recessive inheritance, but it is characterized by a deficiency of multiple
lysosomal enzymes needed to break down carbohydrates.  This disorder is
characterized by such symptoms as claw-like hands, somewhat coarse facial
features, dwarfism, and pain in the hands.  Intelligence tends to be normal
in most patients, but mild mental retardation is sometimes present.

Ganglioside Sialidase Deficiency (ML IV) is a disorder of unknown cause
characterized by early clouding of the cornea, mild to moderate mental
retardation and enlargement of liver and spleen.

Therapies:  Standard

Treatment of Sly Syndrome is symptomatic and supportive.  Surgery may be used
to correct orthopedic problems, and to correct hernias, eye and
cardiovascular problems.

Genetic counseling may be helpful to both patient and family.  Prenatal
diagnosis is now possible for Sly syndrome from the fourth month of pregnancy
on.

Therapies:  Investigational

Since prenatal diagnosis is now possible through amniocentesis and sampling
of a tissue layer in the embryo (chorionic villus sampling), new treatments
aimed at checking early development of Sly Syndrome are now under study.  One
method involves replacing defective enzymes via enzyme replacement therapy
and/or bone marrow transplants.

Scientific study of gene replacement in animal models raises hope that
gene replacement may someday be made available to people with genetic
disorders such as Sly Syndrome.

The Mayo Clinic is investigating the use of Alpha Interferon as a
treatment for Sly Syndrome.  For more information, physicians can contact:

     Morie A. Gertz, M.D.
     Dept. of Hematology & Internal Medicine
     Mayo Clinic
     Rochester, MN  55905
     [phone]

This disease entry is based upon medical information available through
January 1990.  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 Sly Syndrome, 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 Mucopolysaccharide Diseases, Inc.
     382 Parkway Blvd.
     Flin Flon, Manitoba, Canada R8A OK4

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

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

For information on genetics and genetic counseling referrals, please
contact:

     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

MPS Society Brochure.

BIRTH DEFECTS COMPENDIUM, 2nd ed:  Daniel Bergsma, ed; March of Dimes,
1979.  Pp. 734-735.

MENDELIAN INHERITANCE IN MAN, 6th ed:  Victor A. McKusick; Johns Hopkins
University Press, 1983.  Pp. 842-843.