The leukodystrophies are a group of rare genetic disorders
that affect the central nervous system by disrupting the growth
or maintenance of the myelin sheath that insulates nerve cells.
These disorders are progressive, meaning that they tend to get
worse throughout the life of the patient. Below we describe the
source of the disorders in more detail. Fact sheets on the
individual leukodystrophies are also available from the United
Leukodystrophy Foundation.
What is the nervous system?
In order to understand the leukodystrophies, we need to
discuss some basic facts about the nervous system. The nervous
system is made up of two main components: the central nervous
system (CNS) and the peripheral nervous system (PNS). Together,
these two systems interact to carry and receive signals that are
responsible for nearly everything we do, including involuntary
functions such as our heartbeat, and voluntary functions such as
walking.
The CNS consists of the brain and the spinal cord, and
contains billions of specialized cells known as neurons. Neurons
have specialized projections called dendrites and axons that
contribute to their unique function of transmitting signals
throughout the body. Dendrites carry electrical signals to the
neuron, while axons carry them away from the neuron.
The PNS consists of the rest of the neurons in the body.
These include the sensory neurons, which detect any sensory
stimuli and alert the CNS of their presence, and motor neurons,
which connect the CNS to the muscles and carry out instructions
from the CNS for movement.
What is Myelin?
Myelin, sometimes referred to as "white matter" because of
its white, fatty appearance, protects and insulates the axons.
It consists of a protective sheath of many different molecules
that include both lipids (fatty molecules) and proteins. This
protective sheath acts in a manner very similar to that of the
protective insulation that surrounds an electric wire; that is,
it is necessary for the rapid transmission of electrical signals
between neurons. It does this primarily by containing the
electrical molecules within the axon so that they are all
properly transmitted to the next neuron. With the protective
myelin coat, neurons can transmit signals at speeds up to 60
meters per second. When the coat is damaged, the maximum speed
can decrease by ten-fold or more, since some of the signal is
lost during transmission. This decrease in speed of signal
transmission leads to significant disruption in the proper
functioning of the nervous system.
The leukodystrophies are a group of rare genetic disorders
that affect the central nervous system by disrupting the growth
or maintenance of the myelin sheath that insulates nerve cells.
These disorders are progressive, meaning that they tend to get
worse throughout the life of the patient. Below we describe the
source of the disorders in more detail. Fact sheets on the
individual leukodystrophies are also available from the United
Leukodystrophy Foundation.
What is a Leukodystrophy?
The word leukodystrophy comes from the Greek words leuko
(meaning white), trophy (meaning growth), and dys (meaning ill).
If you put these words together, the word leukodystrophy
describes a set of diseases that affect the growth or
maintenance of the white matter (myelin).
How are the leukodystrophies different from
one another?
All leukodystrophies are a result of problems with the growth
or maintenance of the myelin sheath. However, there are many
genes that are important in this process. For example, some
genes are involved with the synthesis of the proteins needed for
the myelin, while others are required for the proper transport
of these proteins to their final location in the myelin sheath
that covers the axons. Defects in any of the genes (called a
mutation) may lead to a leukodystrophy. However, the symptoms of
the individual leukodystrophies may vary because of the
differences in their genetic cause.
How do you get leukodystrophy?
Leukodystrophies are mostly inherited disorders, meaning that
it is passed on from parent to child. They may be inherited in a
recessive, dominant, or X-linked manner, depending on the type
of leukodystrophy. The individual pages on each leukodystrophy
will describe the particular pattern of inheritance for that
disease. There is also a separate fact sheet describing the
different genetic inheritance patterns available from the United
Leukodystrophy Foundation.
There are some leukodystrophies that do not appear to be
inherited, but rather arise spontaneously. They are still caused
by a mutation in a particular gene, but it just means that the
mutation was not inherited. In this case, the birth of one child
with the disease does not necessarily increase the likelihood of
a second child having the disease.
Are the leukodystrophies related to multiple
sclerosis?
The leukodystrophies do share some common features with
multiple sclerosis (MS). Like the leukodystrophies, MS is caused
by the loss of myelin from the axons. However, the cause is
different; whereas leukodystrophies are generally caused by a
defect in one of the genes involved with the growth or
maintenance of the myelin, MS is thought to be caused by an
attack on the myelin by the body’s own immune system.
Pelizaeus-Merzbacher Disease Leukodystrophy (PMD) is a generally nonprogressive, X-linked disorder of the central nervous system (CNS). This means it most often occurs in boys. It is caused by a duplication of or other mutation in the proteolipid protein gene (PLP). Proteolipid protein is the chief protein of the myelin sheaths of the CNS nerve cells. In its more severe form the disease leads to infirmity and, soon after the beginning of the symptoms, to death.
