CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0344/03440.txt

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$Unique_ID{BRK03440}
$Pretitle{}
$Title{Alexander's Disease}
$Subject{Alexander's Disease Leukodystrophy with Rosenthal Fibers
Megalencephaly with Hyaline Inclusion Fibrinoid Degeneration of Astrocytes
Megalencephaly with Hyaline Panneuropathy Fibrinoid Leukodystrophy Hyaline
Panneuropathy Dysmyelogenic Leukodystrophy Dysmyelogenic
Leukodystrophy-Megalobarencephaly Hydrocephalus Multiple Sclerosis
Astrocytoma, Malignant Astrocytoma, Benign Adrenoleukodystrophy Canavan's
Leukodystrophy Metachromatic Leukodystrophy Pelizaeus-Merzbacher Brain
Sclerosis National}
$Volume{}
$Log{}

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

56:
Alexander's Disease

** IMPORTANT **
It is possible that the main title of the article (Alexander's 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

     Leukodystrophy with Rosenthal Fibers
     Megalencephaly with Hyaline Inclusion
     Fibrinoid Degeneration of Astrocytes
     Megalencephaly with Hyaline Panneuropathy
     Fibrinoid Leukodystrophy
     Hyaline Panneuropathy
     Dysmyelogenic Leukodystrophy
     Dysmyelogenic Leukodystrophy-Megalobarencephaly

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

     Hydrocephalus
     Multiple Sclerosis
     Astrocytoma, Malignant
     Astrocytoma, Benign
     Adrenoleukodystrophy
     Canavan's Leukodystrophy
     Metachromatic Leukodystrophy
     Pelizaeus-Merzbacher Brain Sclerosis

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.


Alexander's Disease is an extremely rare, progressive, metabolic,
neurological disorder that is frequently inherited.  It is one of a group of
diseases known as the leukodystrophies.  Alexander's Disease is characterized
by loss of the fatty layers that cover nerves (demyelination), and the
formation of abnormal bodies (Rosenthal fibers) in supporting cells
(astrocytes) of the brain.  These Rosenthal fibers most frequently form on
the surface of the brain and around the blood vessels within the brain.  The
symptoms of Alexander's Disease usually begin during infancy and are
associated with mental and physical retardation.  Juvenile (occuring later
than infancy) and adult-onset Alexander's Disease are recognized forms of
this disorder but occur very infrequently.

Symptoms

The early symptoms of Alexander's Disease that occur during infancy include
muscle spasms and mental as well as physical retardation.  Infants with this
disorder typically have an abnormally large head (megalencephaly), and
failure to thrive.  When symptoms begin in childhood rather than infancy, the
child experiences a progressive loss of previously acquired motor and mental
skills.  As this disease progresses, seizures may occur.

Juvenile-onset Alexander's Disease begins during childhood or adolescence
and generally has a long course.  Symptoms are similar to the infantile form
of this disorder but may also include difficulty swallowing, painful joints,
vomiting, respiratory difficulties, the inability to cough, and/or muscle
spasms.

Alexander's Disease may also begin during adulthood.  There may be few or
no symptoms but abnormal bodies (Rosenthal fibers) in the supporting cells
(astrocytes) appear in the brain.  Computer tomography (CT scan) and magnetic
resonance imaging (MRI) can confirm the presence of Rosenthal fibers and the
diagnosis of this very rare form of leukodystrophy.  Rosenthal fibers are not
exclusively found in Alexander's Disease, but sometimes occur in other
neurological conditions.  If an adult does have symptoms of Alexander's
Disease, they are frequently confused with those of Multiple Sclerosis or the
growth of Benign or Malignant Astrocytes.  (For information on these
diseases, see the related disorders section of this report.)  These symptoms
may include headaches, numbness or tingling in the arms and legs, difficulty
walking, visual impairment, muscle weakness, fatigue, and/or intellectual
impairment.

Causes

The exact cause of Alexander's Disease is not known and the metabolic defect
that causes this disease has not yet been identified.

It is thought that Alexander's Disease may be inherited as an autosomal
recessive genetic trait.  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 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.

Affected Population

Alexander's Disease is an extremely rare disorder that affects males and
females in equal numbers.

Related Disorders

Symptoms of the following disorders can be similar to those of Alexander's
Disease.  Comparisons may be useful for a differential diagnosis:

Hydrocephalus is a condition in which the normal flow of cerebrospinal
fluid (CSF) is restricted and the spaces in the brain (ventricles) become
abnormally enlarged.  Fluid accumulates beneath the skull and puts pressure
on the brain.  Hydrocephalus is characterized in children by an abnormally
enlarged head (megalencephaly).  The scalp may be thin and transparent, and
the forehead may bulge (frontal bossing).  Other symptoms of Hydrocephalus
may include convulsions, abnormal reflexes, a slowed heartbeat, headache,
vomiting, weakness and/or problems with vision.  (For more information on
this disorder, choose "Hydrocephalus" as your search term in the Rare Disease
Database.)

Multiple Sclerosis is a chronic disorder of the central nervous system
(CNS) that causes the destruction of the fatty covering on nerves
(demyelination).  The symptoms of this disease vary greatly and may include
visual impairment, double vision and/or involuntary rhythmic movements of the
eyes (nystagmus), impairment of speech, numbness or tingling sensations in
the arms and legs, muscle weakness and/or difficulty walking.  The symptoms
of Multiple Sclerosis may be similar to those of Adult-Onset Alexander's
Disease.  (For more information on this disorder, choose "Multiple Sclerosis"
as your search term in the Rare Disease Database.)

Astrocytomas are brain tumors that can be either benign or malignant and
are composed of large, star shaped cells (astrocytes).  Symptoms may vary
according to the size, location, and growth rate of the tumor.  Frequently
the first symptom is a recurrent headache that is typically a result of
increased pressure within the skull due to the growth of the tumor.
Headaches may be accompanied by vomiting and/or personality changes.  Other
symptoms of Benign or Malignant Astrocytomas may include irritability,
emotional instability, memory loss, intellectual impairment, convulsions,
paralysis, and/or seizures.  (For more information on this disorder, choose
"Astrocytoma" as your search term in the Rare Disease Database.)

Adrenoleukodystrophy is a form of Leukodystrophy.  It is a rare inherited
metabolic disorder characterized by the accumulation of very long chain fatty
acids (VLCFA) in the brain that causes the progressive loss of the fatty
covering (myelin sheath) on nerves within the brain.  This disorder also
causes progressive degeneration of the adrenal gland (adrenal atrophy).
Symptoms of the childhood form of Adrenoleukodystrophy, which affects only
males, may include loss of previously acquired intellectual skills, poor
memory, loss of emotional control, a jerky uncoordinated walk (ataxia),
and/or muscle weakness on one side of the body.  Other symptoms may include
difficulties with speech, hearing loss, and/or visual impairment.  (For more
information on this disorder, choose "Adrenoleukodystrophy" as your search
term in the Rare Disease Database.)

Canavan's Leukodystrophy is another rare, inherited form of
leukodystrophy characterized by the progressive deterioration of the central
nervous system.  Symptoms of this disorder may include floppiness, the loss
of previously acquired mental and motor skills, poor head control, an
abnormally enlarged head (megalencephaly) and/or blindness.   As Canavan's
Leukodystrophy progresses, there may be spastic muscle contractions in the
arms and legs and paralysis.  This disorder is caused by a chemical imbalance
in the brain and symptoms typically appear in early infancy.  (For more
information on this disorder, choose "Canavan's Leukodystrophy" as your
search term in the Rare Disease Database.)

Metachromatic Leukodystrophy is a rare inherited leukodystrophy
characterized by the abnormal accumulation of a fatty-like substance
(sphingolipid) in the brain and other tissues of the body.  Symptoms of this
disorder may include muscle rigidity, visual impairment, and/or convulsions.
Previously acquired physical and intellectual skills may be lost.  This
disorder may begin in infancy, adolescence, or adulthood.  (For more
information on this disorder, choose "Metachromatic Leukodystrophy" as your
search term in the Rare Disease Database.)

Pelizaeus-Merzbacher Brain Sclerosis is a very rare inherited
leukodystrophy characterized by the degeneration of the brain caused by the
loss of fatty myelin sheath covering the nerves (demyelination).  This
disorder may begin in infancy or adulthood.  The first symptoms in an infant
include failure to thrive, developmental delays, muscle spasms, unsteadiness,
weakness, and/or visual impairment.  Deformities of the bones and convulsions
are sometimes seen.  (For more information on this disorder, choose
"Pelizaeus-Merzbacher" as your search term in the Rare Disease Database.)

Therapies:  Standard

The treatment of Alexander's Disease is symptomatic and supportive.  Genetic
counseling may be of benefit for patients and their families.

Therapies:  Investigational

Current research on Alexander's Disease is focused on identifying the exact
composition of the Rosenthal fibers and the factors responsible for their
formation and growth.  Recent progress has been made in identifying at least
two compounds that are present in Rosenthal fibers.  These findings may
eventually lead to new methods of diagnosis and in time may lead to the
development of new treatments for Alexander's Disease.

Research on birth defects and their causes is ongoing.  The National
Institutes of Health (NIH) is sponsoring the Human Genome Project that 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.

This disease entry is based upon medical information available through
April 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 Alexander's Disease, please contact:

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

     United Leukodystrophy Foundation
     2304 Highland Drive
     Sycamore, IL  60178
     [phone]
     [phone]

     Children's Brain Diseases Foundation
     350 Parnassus, Suite 900
     San Francisco, CA  94117
     [phone]
     [phone]

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

     Association Europeenne contre les Leucodystrophies
     7 Rue Pasteur
     54000 NANCY
     France

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. 1699-1705.

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:
Johns Hopkins University Press, 1992.  Pp. 1207-1208.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 83-84.

PRINCIPLES OF NEUROLOGY, 4th Ed.; Raymond D. Adams, M.D. and Maurice
Victor, M.D., Editors; McGraw-Hill Information Services Company, 1989.  Pp.
789-791, 970-971.

PROGRESSIVE FIBRINOID DEGENERATION OF FIBRILLARY ASTROCYTES ASSOCIATED
WITH MENTAL RETARDATION IN A HYDROCEPHALIC INFANT:  W.S. Alexander:  Brain
(Issue 1949:72).  Pp. 373-381.

ALEXANDER'S DISEASE.  D. Borrett.  Brain (Jun 1985; 108(Pt 2)).  Pp. 367-
385.