CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0383/03833.txt

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$Unique_ID{BRK03833}
$Pretitle{}
$Title{Hurler Syndrome}
$Subject{Hurler Syndrome Mucopolysaccharidosis Type I MPS Disorder MPS I
Gargoylism Hurler Disease Mucopolysaccharidosis I-H Scheie Syndrome
Mucopolysaccharidosis I-S Hurler-Scheie Syndrome}
$Volume{}
$Log{}

Copyright (C) 1986, 1987, 1988, 1990, 1991 National Organization for Rare
Disorders, Inc.

284:
Hurler Syndrome

** IMPORTANT **
It is possible the main title of the article (Hurler 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 Type I
     MPS Disorder
     MPS I
     Gargoylism

DISORDER SUBDIVISIONS

     Hurler Disease, also known as Mucopolysaccharidosis I-H
     Scheie Syndrome, also known as Mucopolysaccharidosis I-S
     Hurler-Scheie Syndrome

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.  Hurler Syndrome is a form of
MPS.

Symptoms

There are three forms of Hurler Syndrome with varying severity.  All are due
to alpha-L-iduronidase deficiency.  Infants with Hurler Syndrome usually
appear normal at birth, but may have inguinal and umbilical hernias.  The
diagnosis of Hurler Syndrome is commonly made between 6 and 24 months of age
when the patient may exhibit coarse facial features, clouding of the cornea,
enlarged liver and spleen, a large tongue, skeletal abnormalities, poor
growth, joint stiffness, and a prominent forehead.

Hurler Syndrome is characterized by high concentrations of
mucopolysaccharides, dermatan and heparan sulfates, in the urine.  It is the
most severe form.  Symptoms first become evident at 6 months to 2 years of
age with developmental delay, recurrent urine and upper respiratory
infections, noisy breathing and a persistent nasal discharge.  Hydrocephalus
is commonly present after the age of 2-3 years.  (For more information on
this disorder, choose "hydrocephalus" as your search term in the Rare Disease
Database.)  Other physical manifestations of this disorder may include
clouding of the cornea of the eye, unusually large tongue, misaligned teeth,
the development of a curved back and severe joint stiffness with clawlike
hands.  Mental development of Hurler syndrome usually reaches a peak at about
2 years of age with progressive mental retardation thereafter.

The milder form of Hurler Syndrome is known as Scheie syndrome.  These
patients have normal intelligence, stature and life expectancy, but suffer
from physical symptoms such as stiff joints, clouding of the cornea, and flow
of blood from the aorta back into the left ventricle of the heart (aortic
regurgitation).  The onset of symptoms in patients with Scheie syndrome
usually occurs after the age of 5 years.  However, diagnosis is commonly
delayed to between 10 to 20 years of age.

Hurler-Scheie syndrome is an intermediate form 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.

Causes

Hurler Syndrome in all three of its variations is transmitted genetically,
with each parent contributing one recessive gene carrying exactly the same
type of genetic inheritance.  (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.)

The enzyme that is normally present to break down the carbohydrates
(mucopolysaccharides) that is missing in Hurler Syndrome I is
alpha-L-iduronidase.

Affected Population

Hurler Syndrome tends to affect males and females equally with an incidence
of about 1 in 100,000 live births.

Related Disorders

There are many types of Mucopolysaccharidoses.  For more information on these
diseases, choose "MPS Disorder" as your search term in the Rare Disease
Database.

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 (mucopolysaccharidosis VIII) is not a valid
medical disorder.

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

Therapies:  Standard

Treatment of Hurler Syndrome is symptomatic and supportive.  Physical
therapy, medical and genetic counseling services will be useful to patient
and family.  Prenatal diagnosis is now possible for this disorder.

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 MPS including Hurler 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 the hope that gene replacement therapy
may someday be made available to people with genetic disorders such as MPS.

Scientists are beginning to study fetal tissue transplants in children
with Hurler Syndrome.  Earlier studies in animals showed promising results
with this form of trestmernt, but there is no way to predict that this will
work in humans.

The Mayo Clinic is investigating the use of Alpha Interferon as a
treatment for Hurler 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
November 1991.  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 Hurler 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]

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

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.

MPS Research Funding Center Bulletin.

BIRTH DEFECTS COMPENDIUM, 2nd ed.:  Daniel Bergsma; March of Dimes, 1979.
Pp. 727-729.