CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0412/04124.txt

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$Unique_ID{BRK04124}
$Pretitle{}
$Title{Pompe Disease}
$Subject{Pompe Disease Acid Maltase Deficiency Alpha-1,4 Glucosidase
Deficiency Von Gierke Disease Forbes Disease McArdle Disease Tarui Disease
Andersen Disease Werdnig-Hoffmann Disease}
$Volume{}
$Log{}

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

404:
Pompe Disease

** IMPORTANT **
It is possible the main title of the article (Pompe Disease) is not the
name you expected.  Please check the SYNONYMS listing on the next page to
find alternate names, disorder subdivisions, and related disorders covered by
this article.

Synonyms

     Acid Maltase Deficiency
     Alpha-1,4 Glucosidase Deficiency
     Cardiomegalia Glycogenica Diffusa
     Generalized Glycogenosis
     Glycogen Storage Disease Type II
     Glycogenosis Type II
     Lysosomal Glucosidase Deficiency

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

     Von Gierke Disease
     Forbes Disease
     McArdle Disease
     Tarui Disease
     Andersen Disease
     Werdnig-Hoffmann 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.


Pompe Disease is a glycogen storage disease.  This hereditary metabolic
disorder is caused by an inborn lack of the enzyme alpha-1,4 glucosidase
(lysosomal glucosidase; acid maltase).  This enzyme deficiency causes excess
amounts of glycogen to accumulate in the lysosomes of all body tissues, due
to an inability to break down the glycogen.  The glycogen accumulates in the
lysosomes, which swell and cause cell damage or death.

Symptoms

Pompe Disease occurs in different degrees of severity, and onset can occur at
various ages.

INFANTILE FORM:
Onset of symptoms usually occurs at 2 to 5 months of age, but the child
may be affected at birth.  Severe muscle weakness without muscle wasting
usually occurs within the first few months of life.  An enlarged heart
(cardiomegaly), enlarged liver (hepatomegaly), and enlarged tongue
(macroglossia) also occurs.  Progressive cardiac failure usually causes death
by 12 to 18 months of age.

CHILDHOOD FORM:
This form of Pompe Disease usually begins in late infancy or early
childhood.  The disorder progresses more slowly than the early infantile
form.  The extent of organ involvement varies between patients but skeletal
muscle weakness is usually present with minimal cardiac involvement.  Life
expectancy for children with this form of the disorder is longer than for the
infantile form with survival into the second decade.

ADULT FORM:
Symptoms of the adult onset form of Pompe Disease include muscle weakness
such as that found in other chronic muscle disorders.  Onset of symptoms
usually occurs in the second to fourth decade.  This form of the disorder is
slowly progressive without cardiac involvement, and life expectancy is
usually normal.

Causes

Pompe Disease is a disorder inherited through autosomal recessive genes.
Symptoms are caused by a lack of the enzyme alpha-1,4 glucosidase (lysosomal
glucosidase; acid maltase) which is needed for glycogen breakdown in the
lysosomes.  This enzyme deficiency causes an increased concentration of
glycogen in body tissues (mainly the muscles) and causes cell damage
resulting in muscle weakness.  Patients with Type II Glycogen Storage Disease
do not have problems with too little sugar (hypoglycemia) in the blood in
contrast to other types of glycogen storage disorders (e.g., Type I and Type
III.)

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

Pompe Disease and all other glycogen storage disorders together affect less
than 1 in 40,000 persons in the United States.  Males and females are
affected in equal numbers.  While most cases involve infants and children,
some slowly progressive adult cases have been described in the medical
literature.

Related Disorders

Most Glycogen Storage Diseases are inborn errors of metabolism in which the
balance between stored energy (glycogen), and available energy (sugar or
glucose), is disturbed.  In some of these disorders the breakdown of glycogen
into sugar is slowed.  Too much glycogen tends to be stored in the liver and
muscles, and too little sugar is available in the blood.  In other Glycogen
Storage Diseases, glucose cannot be built up into glycogen again.  This
results in an increased level of glucose in the blood.

The following diseases are similar to Pompe Disease.  These can be
compared to Pompe Disease for a differential diagnosis:

Von Gierke Disease is a glycogen storage disease.  This hereditary
metabolic disorder is caused by an inborn lack of either the enzyme glucose-
6-phosphatase or the enzyme glucose-6-phosphate translocase.  These enzymes
are needed to convert the main carbohydrate storage material (glycogen) into
sugar (glucose) which the body uses for its energy needs.  A deficiency of
these enzymes causes abnormal deposits of glycogen in the liver and kidney
cells.  (For more information on this disorder, choose "Von Gierke" as your
search term in the Rare Disease Database.)

McArdle Disease is a glycogen storage disease.  Symptoms of this
hereditary metabolic disorder are caused by an inborn lack of the enzyme
myophosphorylase.  This enzyme is needed for the breakdown of glycogen (the
body's form of stored energy) into sugar (glucose).  Glucose is normally
released as glucose-1-phosphate during strenuous exercise when the muscles
need energy.  In McArdle Disease the breakdown of glucose cannot take place
and severe muscle cramps occur as a result of heavy exercise.  (For more
information on this disorder, choose "McArdle" as your search term in the
Rare Disease Database.)

Tarui Disease (Phosphofructokinase Deficiency) is another type of
glycogen storage disease.  Symptoms of this genetic metabolic disorder are
caused by an inborn lack of the enzyme fructophosphokinase in muscle, and a
partial deficiency of this enzyme in red blood cells.  The deficiency
prevents the breakdown of glucose into energy.  Tarui Disease is
characterized by pain and muscle cramps during muscle stress, but usually
causes less severe symptoms than McArdle Disease.  (For more information on
this disorder, choose "Tarui" as your search term in the Rare Disease
Database.)

Forbes Disease (Glycogenosis III; Cori Disease) is another glycogen
storage disease inherited through autosomal recessive genes.  Symptoms are
caused by a lack of the enzyme amylo-1,6 glucosidase.  This enzyme deficiency
causes excess amounts of glycogen (the stored form of energy from
carbohydrates) to be deposited in the liver, muscles, and heart.  The nerves
on the back of the legs and on the sides of the heel and foot (sural nerves)
also accumulate excess glycogen.  (For more information on this disorder,
choose "Forbes" as your search term in the Rare Disease Database.)

Andersen Disease is a glycogen storage disease inherited through
recessive genes.  Symptoms of this metabolic disorder are caused by a lack of
the brancher enzyme amylo transglucosidase.  The deficiency of this enzyme
causes an abnormality in the structure of the main carbohydrate storage
material (glycogen).  This structural abnormality of glycogen is thought to
trigger the body's immune system.  Consequently the immune system attacks the
glycogen in the liver, spleen and muscles where glycogen is primarily stored.
Andersen Disease is characterized by scarring of the liver (cirrhosis) which
may lead to liver failure.  (For more information on this disorder, choose
"Andersen" as your search term in the Rare Disease Database.)

Werdnig-Hoffmann Disease (Infantile Spinal Muscular Atrophy) is a severe
and usually rapidly progressive neuromuscular disorder that is not related to
glycogen storage diseases.  It is inherited as a recessive trait and usually
begins during infancy.  Werdnig-Hoffmann Disease is characterized by a
generalized flaccid and symmetrical wasting (atrophy) and weakness of the
muscles of the trunk and extremities.  Symptoms may be caused by degenerative
changes in certain nerve cells of the spinal cord (ventral horn cells).  This
weakness, known as the amyotonia congenita syndrome, is also found in other
neuromuscular disorders.  A rapidly progressive form of this condition
affects infants, whereas a more slowly progressive form affects adults.
("For more information on this disorder, choose "Werdnig" as your search term
in the Rare Disease Database.)

Therapies:  Standard

Prenatal diagnosis of Pompe Disease is possible by testing the activity of
the enzyme alpha-1,4 glucosidase in cells cultured from the mother's amniotic
fluid.  Diagnosis after birth can be made by testing enzyme activity in white
blood cells, as well as the glycogen concentration in muscle cells.

Treatment of Pompe Disease is symptomatic and supportive.  Attempts at
enzyme replacement have been tried, but have not been successful to date.
Genetic counseling will be helpful to the families of children with Pompe
Disease.

Therapies:  Investigational

Dr. Y.T. Chen at Duke University Medical Center, at the request of the
Glycogen Storage Disease Association, is collecting DNA from patients with
Glycogen Storage Disease Type I to form a DNA bank for GSDI.  Interested
patients may contact the Glycogen Storage Diseases Association for further
information.  The address and phone number of the organization are listed in
the Resources section of this report.

This disease entry is based upon medical information available through
February 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 Pompe Disease, please contact:

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

     Association for Glycogen Storage Diseases
     Box 896
     Durant, IA  52747
     [phone]

     Research Trust for Metabolic Diseases in Children
     Golden Gates Lodge, Weston Rd.
     Crewe CW1 1XN, England
     Telephone:  [phone]

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

     Dr. Alfred Slonim
     Center for Inborn Errors of Metabolism
     North Shore University Hospital
     Manhasset, NY  11030

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

THE MERCK MANUAL 15th ed:  R. Berkow, et al:  eds; Merck, Sharp & Dohme
Research Laboratories, 1987.  Pp. 1453.

CECIL TEXTBOOK OF MEDICINE, 18th ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Eds.:  W. B. Saunders Co., 1988.  Pp. 361, 1134.