CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0393/03937.txt

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$Unique_ID{BRK03937}
$Pretitle{}
$Title{Leukodystrophy, Krabbe's}
$Subject{Leukodystrophy Krabbe's Galactocerebrosidase Deficiency Galactoside
Beta-Galactosidase Deficiency Galactosylceramidase Deficiency Galactosyl
Ceramide Lipidosis Globoid Leukodystrophy Krabbe's Disease Leukodystrophy
Globoid Cell Sphingolipidosis Adrenoleukodystrophy Canavan's Leukodystrophy
Metachromatic Leukodystrophy Alexander's Disease }
$Volume{}
$Log{}

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

379:
Leukodystrophy, Krabbe's

** IMPORTANT **
It is possible the main title of the article (Krabbe's Leukodystrophy) 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

     Galactocerebrosidase Deficiency
     Galactoside Beta-Galactosidase Deficiency
     Galactosylceramidase Deficiency
     Galactosyl Ceramide Lipidosis
     Globoid Leukodystrophy
     Krabbe's Disease
     Leukodystrophy, Globoid Cell
     Sphingolipidosis

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

     Adrenoleukodystrophy
     Canavan's Leukodystrophy
     Metachromatic Leukodystrophy
     Alexander's 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.

Krabbe's Leukodystrophy is a very rare hereditary lipid storage disorder
caused by a deficiency of the enzyme galactoside beta-galactosidase
(galactosyl-ceramidase).  This causes the myelin sheath surrounding nerves in
the brain to degenerate (demyelination).  Characteristic globoid cells appear
in affected areas of the brain.  This metabolic disorder is characterized by
progressive neurological dysfunction such as mental retardation, paralysis,
blindness, deafness and pseudobulbar palsy.

Symptoms

Onset of Krabbe's Leukodystrophy in the predominant infantile form (90% of
cases) occurs between 3 and 5 months of age.  A late-onset form of the
disorder occurs at 18 months or a later age.

Infants affected by Krabbe's Leukodystrophy are fretful and apathetic.
Vomiting and partial unconsciousness are other possible symptoms.  The lower
extremities may have spastic contractions.  Seizures characterized by
alternating contraction and relaxation (clonic), or by continuous tension
(tonic), may also occur.  Affected infants are hypersensitive to sounds and
noises.  Mental and physical development may be slow.  Because of
degeneration of certain parts of the brain, the legs are sometimes rigidly
extended at the hip and knee; the arms may be rotated at the shoulder and
extended at the elbow; and the ankles, toes and fingers may be flexed
(decerebrate rigidity).  Blindness caused by brain cortex degeneration may
also occur.  Patients with Krabbe's Leukodystrophy may also have difficulty
swallowing (dysphagia).

Causes

Krabbe's Leukodystrophy is a hereditary disorder transferred to offspring
through recessive genes.  It is caused by a deficiency of the enzyme
galactoside beta-galactosidase (galactosyl ceramidase).  This enzyme is
needed for the metabolism of galactocerebroside (galactosyl ceramide), a
component of the fatty sheath around the nerves (myelin).  The demyelination
of the nerve cells in the large hemispheres of the brain (and in the brain
stem) causes the neurological symptoms of Krabbe's Leukodystrophy.

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

About 1 in 40,000 newborn babies in the United States is affected with
Krabbe's Leukodystrophy.  Males are affected as often as females.

Related Disorders

There are many related forms of Leukodystrophy.  For more information on
these disorders, choose "Leukodystrophy" as your search term in the Rare
Disease Database.

Adrenoleukodystrophy (ALD, or Schilder's Disease) is one of many
different leukodystrophies.  The disorder may appear in two distinct genetic
forms:  sex-linked and Neonatal ALD.  Both are characterized by destruction of
the lipid sheaths surrounding the nerves (demyelination) in the brain.
However, they differ in the mode of inheritance, severity and type of
symptoms.  All types of ALD are characterized by an accumulation of Very Long
Chain Fatty Acids (VLCFA), which is a type of fat molecule that accumulates
in the body's tissues, especially in the adrenal gland and the white matter
of the brain.  An accumulation of lymph and plasma cells around the blood
vessels in the central nervous system may also occur.

Canavan's Leukodystrophy (Spongy Degeneration of the Brain) is a form of
leukodystrophy which causes the white matter of the brain to be replaced by
microscopic fluid-filled spaces.  This disorder, a hereditary disease in
children, is characterized by structural abnormalities and deterioration of
motor, sensory, and intellectual functions.  It seems to affect persons of
Eastern European Jewish ancestry most frequently.  The disorder is
progressive and degenerative.

Metachromatic Leukodystrophy (MLD) is an autosomal recessive inherited
disease which affects the brain and spinal cord.  The disease is
characterized by progressive paralysis and dementia.

Alexander's Disease is an infantile form of leukodystrophy characterized
by an enlarged brain, mental retardation, failure to thrive, spasticity and
possibly seizures.

For more information on the above disorders, choose
"Adrenoleukodystrophy," "Canavan," "MLD," and "Alexander" as your search
terms in the Rare Disease Database.

Therapies:  Standard

Krabbe's Leukodystrophy can be diagnosed by testing the activity of the
enzyme galactocerebrosidase (galactosylceramidase) in fibroblast cells
obtained from an infant or from a fetus by amniocentesis.

Treatment for Krabbe's Leukodystrophy is symptomatic and supportive.
Genetic counseling may be helpful for families of children affected by this
illness.

Therapies:  Investigational

Current research is directed toward the identification and cloning of genes,
and defining the specific gene abnormality responsible for the
leukodystrophy.  Bone marrow transplantation is being researched as a
possible treatment for Krabbe's Leukodystrophy patients.  This involves
extracting cross-matched bone marrow from a healthy donor and injecting it
into a patient.  The healthy bone marrow cells enter the general circulation
and migrate through the blood to marrow cavities in the patient's bones.  The
new marrow cells begin to grow and produce new white blood cells and
platelets.  This procedure involves risks which must be balanced against
possible benefits.  It is used experimentally in the most severe cases of
this disorder.

Bone marrow transplantation is being tested as a treatment for infantile
Krabbe's Leukodystrophy.  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 procedure.

This disease entry is based upon medical information available through
March 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 Krabbe's Leukodystrophy, 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]

     Adrenoleukodystrophy (ALD) Project
     Hugo M. Moser, M.D.
     John F. Kennedy Institute
     707 North Broadway
     Baltimore, MD  21205
     [phone]

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

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

     Association Europeenne contre les Leucodystrophies
     7 Rue Pasteur
     54000 NANCY
     France

For more 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

A CORRELATIVE SYNOPSIS OF THE LEUKODYSTROPHIES:  P. Morell; Neuropediatrics
(September 1984:  Suppl. 15).  Pp. 62-65.

PRENATAL DIAGNOSIS OF KRABBE DISEASE USING A FLUORESCENT DERIVATIVE OF
GALACTOSYLCERAMIDE:  M. Zeigler, et al.; Clinica Chimica Acta (October 15,
1984:  issue 142,3).  Pp. 313-318.