CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0376/03768.txt

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$Unique_ID{BRK03768}
$Pretitle{}
$Title{Gaucher Disease}
$Subject{Acid Beta-glucosidase deficiency Familial Splenic Anemia Cerebroside
Lipidosis Cerebrosidosis Gaucher-Schlagenhaufer Glucocerebrosidase deficiency
Glucocerebrosidosis Glucosyl Ceramide Lipidosis Histiocytosis, lipid, kerasin
type Norrbottnian Gaucher Disease Type I Gaucher Disease also known as
Non-Neuronopathic Chronic, Adult Gaucher Disease or Noncerebral Juvenile
Gaucher Disease Type II Gaucher Disease also known as Neuronopathic Acute or
Infantile Gaucher Disease Type III Gaucher Disease also known as Subacute
Neuronopathic, Juvenile Sandhoff Disease Hajdu-Cheney Syndrome Hepatic
Fibrosis, Congenital Osteonecrosis}
$Volume{}
$Log{}

Copyright (C) 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1992, 1993
National Organization for Rare Disorders, Inc.

12:
Gaucher Disease

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

Synonyms

     Acid Beta-glucosidase deficiency
     Familial Splenic Anemia
     Cerebroside Lipidosis
     Cerebrosidosis
     Gaucher-Schlagenhaufer
     Glucocerebrosidase deficiency
     Glucocerebrosidosis
     Glucosyl Ceramide Lipidosis
     Histiocytosis, lipid, kerasin type
     Norrbottnian Gaucher Disease

DISORDER SUBDIVISIONS:

Type I Gaucher Disease also known as Non-Neuronopathic Chronic, Adult
Gaucher Disease or Noncerebral Juvenile Gaucher Disease

Type II Gaucher Disease also known as Neuronopathic Acute or Infantile
Gaucher Disease

Type III Gaucher Disease also known as Subacute Neuronopathic, Juvenile
Gaucher Disease, or Adult Cerebral Gaucher Disease

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

     Sandhoff Disease
     Hajdu-Cheney Syndrome
     Hepatic Fibrosis, Congenital
     Osteonecrosis

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.


Gaucher disease is the most common of the lipid storage diseases (which
include Tay-Sachs, Fabry's, and Neimann-Pick diseases).  Lipids are various
fats or fat-like substances in the body.  Lipids are stored by the body to be
used as energy at a later time.  There are three forms of Gaucher disease:
Type I (nonneuroleptic); Type II (acute neuroleptic, or infantile cerebral);
Type III (subacute neuroleptic).  Major symptoms include a swollen abdomen,
bone deterioration and acute attacks of bone pain.

Symptoms

In Type I Gaucher disease, bone deterioration is the most common symptom.
Other symptoms include gross enlargement of the liver (hepatomegaly) and/or
the spleen (splenomegaly) and a low level of iron in the red blood cells
(anemia).  People with Gaucher disease usually appear to have a very swollen
abdomen due to enlarged internal organs.

In Type II Gaucher disease, patients may have an enlarged liver and/or
spleen and symptoms that involve the central nervous system (neurological
manifestations).  The symptoms may include overextension (hyperextension) of
the neck, a stiff neck, general feeling of tiredness, and an inability to
move and respond appropriately to outside stimulus (catatonia).  The eyes may
be crossed (strabismus) and there may be an increase in the deep reflexes of
the body.  Patients with Type II Gaucher may also have muscle spasms in the
voice box (laryngismus).  Mental retardation may also be present.

In Type III Gaucher disease, patients usually experience symptoms that
are similar to those of Type I but also include central nervous system
symptoms.  These may include seizures, mental retardation, and abnormal
movements of the eyes, arms, legs, and head.

A diagnostic test is available to detect affected people and carriers of
this disorder.  This condition may also be diagnosed in pregnant women by
testing the cells in the fluid that surrounds the fetus (amniocentesis).

Causes

Most types of Gaucher disease are inherited as an autosomal recessive trait.
Symptoms develop due to a failure to produce a sufficient amount of the
enzyme glucocerebrosidase.

All three different types of Gaucher disease are characterized by the
presence of fat laden "Gaucher cells".  As seen under a microscope, the cells
appear very large and round and have the appearance of wrinkled tissue paper
or "crumpled silk".

The defective gene that causes Gaucher disease and controls the enzyme
glucocerebrosidase is thought to be located at the q21-q31 region of
chromosome 1.  It is thought that different mutations in this gene are
associated with different types of Gaucher disease.

In 1991 an atypical autosomal dominant form of Gaucher was identified in
a female patient.

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 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 not show 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.

In dominant disorders, a single copy of the disease gene (received from
either the mother or father) will be expressed "dominating" the normal gene
and resulting in appearance of the disease.  The risk of transmitting the
disorder from affected parent to offspring is 50% for each pregnancy
regardless of the sex of the resulting child.)

Affected Population

Gaucher disease Type I affects males and females in equal numbers.  Onset can
be at any age although most people are in their late teens when they are
initially diagnosed.  A high proportion of Ashkenazi Jews are affected with
this disorder.

Type II Gaucher disease is a rarer form with symptoms that usually appear
in the first few months of life.  Both males and females can have this
disorder although a slightly higher number of males are diagnosed than
females.

Type III is the rarest form of Gaucher disease.  The age of onset can be
highly variable but generally begins in during childhood or adolescence.  Both
sexes can be affected.

It has been estimated that all types of Gaucher disease together may
affect between 20,000 to 40,000 people worldwide.

Related Disorders

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

Sandhoff Disease is a severe form of Tay-Sachs disease.  It is a
progressive, inherited, lipid storage disorder that leads to the destruction
of the central nervous system.  The first symptoms usually occur in the third
to sixth month of life.  These symptoms may include feeding problems, general
tiredness (lethargy) and a marked "startle" response to sounds.  Cherry red
spots are usually seen on the skin.  (For more information on this disorder,
choose "Sandhoff Disease" as your search term on the Rare Disease Database).

Hajdu-Cheney Syndrome is a rare disorder that affects the tissue that
supports and joins other body tissue and organs (connective tissue).  The
most distinctive symptom of this disorder is a condition in which the palms
of the hands and the soles of the feet have ulcerating tissue (lesions).
This occurs along with a softening and destruction of the bones.  There may
also be abnormal development of other bones, joints and teeth.  There is a
decrease in bone mass and changes in the skull and jawbone.  (For more
information on this disorder, choose "Hajdu-Cheney" as your search term in
the Rare Disease Database).

Hepatic Fibrosis (Congenital) is a rare inherited disorder that affects
both the liver and the kidneys.  The symptoms, which usually occur in
childhood, may include a swollen abdomen, a firm enlarged liver
(hepatomegaly), and the vomiting of red blood due to bleeding in the stomach
and intestines.  Although liver function tests are usually normal, a biopsy
can reveal the presence of fiberlike connective tissue that spreads through
the liver.  (For more information on this disorder, choose "Hepatic Fibrosis"
as your search term in the Rare Disease Database).

OSTEONECROSIS is a slowly progressive disorder of bone destruction.  It
is often due to inadequate blood supply to a bone.  The ends of the long
bones are the most commonly affected (i.e. femur and humerus).  This disorder
may cause pain in the hips, knees, and shoulders.  This pain generally occurs
when standing, walking or lifting.  The pain may worsen and eventually be
present during rest or sleep.  Other symptoms may include muscle spasms,
joint stiffness, and a limitation of range of movement.  (For more
information on this disorder, choose "Osteonecrosis" as your search term in
the Rare Disease Database).

Therapies:  Standard

Treatment of Gaucher Disease may involve the removal of the spleen
(splenectomy) if circumstances warrant it.  Joint replacements for hips,
knees, ankles, shoulders, elbows and wrists may also be considered if bone
destruction has occurred.

The orphan drug Ceredase (glucocerebrosidase/beta-glucosidase), which is
a placenta-derived enzyme, was approved by the FDA in April 1991 for the
treatment of Type I Gaucher disease.  For further information physicians may
contact:

     Genzyme Corp.
     75 Kneeland St.
     Boston, MA 02111
     [phone]

Genetic counseling and testing may be of benefit for patients and their
families.

Therapies:  Investigational

Dr. Edward Ginns is developing a biotechnology version of the enzyme (PEG-
glucocerebrosidase) that may last longer in the body, thereby reducing the
cost to people with Gaucher Disease.  Dr. Ginns is searching for patients who
are not taking Ceredase who might be interested in participating in this
clinical trial.  For more information, please contact:

     Dr. Edward Ginns
     Section on Molecular Neurogenetics, Clinical Neuroscience Branch
     Bldg. 10, Rm. 4N214
     NIH/National Intstitute of Mental Health (NIMH)
     Bethesda, MD  20892
     [phone]

A clinical research program has been established at the National
Institutes of Health in Bethesda, Maryland, to study neurogenetic and
lysosomal storage disorders.  Gaucher Disease is a high priority of this
group of diseases, including mucopolysaccharidoses, glycogen storage
disorders, and other related neurogenetic diseases.  The goal of this program
is to further the fundamental understanding of inherited diseases as an
approach to improved diagnosis and treatment.  Patients included in these
studies may be evaluated at the Genetics Clinic as well as the Molecular
Neurogenetics Unit, Clinical Neuroscience Branch, National Institute of
Mental Health (NIMH), and the Human Genetics Branch of the National Institute
of Child Health and Human Development (NICHHD).

For further information, please contact:

     Patient Care Coordinator
     Human Genetics Branch
     NIH/National Institute of Child Health and Human Development (NICHD)
     Bethesda, MD  20892
     [phone]

Research is ongoing in the areas of recombinant DNA, bone marrow
transplantation, gene therapy and enzyme replacement therapy, the mechanism
of action of the heat-stable activator protein, and cloning.  A new form of
the enzyme is being developed through biotechnological engineering, and is
being tested in clinical trials.  Contact:

     NIH/National Institutes of Health
     Building 10, Rm. 4N248
     9000 Rockville Pike
     Bethesda, MD 20982
     [phone]

Bone marrow transplantation is being tested as a treatment for Gaucher
Disease.  Bone marrow transplantation is not recommended for patients with
relatively advanced neurological symptoms.  More research is needed to
determine the safety and effectiveness of this treatment.

     Other clinical research is being pursued at:
     University of Pittsburgh Medical School
     Dept. of Biochemistry
     Pittsburgh, PA  15261
     [phone]
     Att: Robert Glew, M.D.
     RESEARCH:  Characterization of lipid requirements of enzymes and
investigation of the mechanism of action of the heat-stable activator
protein.

     Scripps Research Institute
     10666 N. Torrey Pine Road
     La Jolla, CA  92037
     [phone]
     Att:  Ernest Beutler, M.D.
     RESEARCH:  Studying protein defects of enzymes using antibodies and
monoclonal antibodies, cloning enzyme genes, developing method for
introducing genes back into protein's cells, and treating patients with low
doses of Ceredase.

     Mount Sinai Hospital
     Division of Medical Genetics
     Annenberg Building, Room 17-76
     100th Street and 5th Avenue
     New York, NY  10029
     Att:  Robert Desnick, M.D.
     RESEARCH:  Replacement enzymes in bone marrow transplantations.

Robert E. Lee, M. D. of the University of Pennsylvania is compiling a
database dealing with the disease.  Contact:

     University of Pittsburgh Medical School
     Dept. of Pathology
     Pittsburgh, PA  15261
     Att:  Robert E. Lee, M. D.

Research on birth defects and their causes is ongoing.  The National
Institutes of Health (NIH) is sponsoring the Human Genome Project which is
aimed at mapping every gene in the human body and learning why they sometimes
malfunction.  It is hoped that this new knowledge will lead to prevention and
treatment of genetic disorders in the future.

A clinical trial using human glucocerebrosidase for treatment of
Gaucher's Disease is being organized by Drs. Ellen Sidransky and Edward Ginns
at NIMH.  The PEG-glucocerebrosidase is being developed by Enzon, Inc., and
has received orphan drug status.  It is hoped that PEG-glucocerebrosidase
will lead to a decrease in symptoms.

For further information, please contact:

     Ms. E. Alzona, Clinical Neuroscience Branch
     Bldg. 10, Rm. 3N 256
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]
     FAX [phone]

This disease entry is based upon medical information available through
March 1993.  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 Gaucher disease, please contact:

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

     Gaucher Disease Foundation
     19241 Montgomery Village Ave., Suite E21
     Gaithersburg, MD  20879
     [phone]

     Tay-Sachs & Allied Diseases Association, Inc.
     2001 Beacon Street, Rm. 304
     Brookline, MA 02164
     [phone] or [phone]

     NIH/National Institute of Neurological Disorders & Stroke (NINDS)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]
     [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

MENDELIAN INHERITANCE IN MAN, 9th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1990.   Pp. 1200-1204.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 1091-1092.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 769-770.

GAUCHER'S DISEASE:  NEW MOLECULAR APPROACHES TO DIAGNOSIS AND TREATMENT,
E. Buetler; Science (May 1992; 256 (5058)):  Pp. 794-799.