Batten disease is a fatal, inherited disorder of the nervous system
that begins in childhood. Early symptoms of this disorder usually appear
between the ages of 5 and 10, when parents or physicians may notice a
previously normal child has begun to develop vision problems or seizures.
In some cases the early signs are subtle, taking the form of personality
and behavior changes, slow learning, clumsiness, or stumbling. Over time,
affected children suffer mental impairment, worsening seizures, and
progressive loss of sight and motor skills. Eventually, children with
Batten disease become blind, bedridden, and demented. Batten disease is
often fatal by the late teens or twenties.
Batten disease is named after the British pediatrician who first
described it in 1903. Also known as Spielmeyer-Vogt-Sjogren-Batten
disease, it is the most common form of a group of disorders called
neuronal ceroid lipofuscinoses (or NCLs). Although Batten disease is
usually regarded as the juvenile form of NCL, some physicians use the term
Batten disease to describe all forms of NCL.
There are three other main types of NCL, including two forms that begin
earlier in childhood and a very rare form that strikes adults. The
symptoms of these three types are similar to those caused by Batten
disease, but they become apparent at different ages and progress at
- Infantile NCL (Santavuori-Haltia disease) begins between about 6
months and 2 years of age and progresses rapidly. Affected children fail
to thrive and have abnormally small heads (microcephaly). Also typical are
short, sharp muscle contractions called myoclonic jerks. Patients usually
die before age 5, although some have survived in a vegetative state a few
- Late infantile NCL (Jansky-Bielschowsky disease) begins between ages 2
and 4. The typical early signs are loss of muscle coordination (ataxia)
and seizures that do not respond to drugs. This form progresses rapidly
and ends in death between ages 8 and 12.
- Adult NCL (Kufs disease or Parry's disease) generally begins before
the age of 40, causes milder symptoms that progress slowly, and does not
cause blindness. Although age of death is variable among affected
individuals, this form does shorten life expectancy
Batten disease and other forms of NCL are relatively rare, occurring in
an estimated 2 to 4 of every 100,000 live births in the United States.
These disorders appear to be more common in Finland, Sweden, other parts
of northern Europe, and Newfoundland, Canada. Although NCLs are classified
as rare diseases, they often strike more than one person in families that
carry the defective genes.
Childhood NCLs are autosomal recessive disorders; that is, they occur
only when a child inherits two copies of the defective gene, one from each
parent. When both parents carry one defective gene, each of their children
faces a one in four chance of developing NCL. At the same time, each child
also faces a one in two chance of inheriting just one copy of the
defective gene. Individuals who have only one defective gene are known as
carriers, meaning they do not develop the disease, but they can pass the
gene on to their own children. Because the mutated genes that are involved
in certain forms of Batten disease are known, carrier detection is
possible in some instances.
Adult NCL may be inherited as an autosomal recessive or, less often, as
an autosomal dominant disorder. In autosomal dominant inheritance, all
people who inherit a single copy of the disease gene develop the disease.
As a result, there are no unaffected carriers of the gene.
Symptoms of Batten disease and other NCLs are linked to a buildup of
substances called lipofuscins (lipopigments) in the body's tissues. These
lipopigments are made up of fats and proteins. Their name comes from the
technical word lipo, which is short for "lipid" or fat, and from the term
pigment, used because they take on a greenish-yellow color when viewed
under an ultraviolet light microscope. The lipopigments build up in cells
of the brain and the eye as well as in skin, muscle, and many other
tissues. Inside the cells, these pigments form deposits with distinctive
shapes that can be seen under an electron microscope. Some look like
half-moons, others like fingerprints. These deposits are what doctors look
for when they examine a skin sample to diagnose Batten disease.
The biochemical defects that underlie several NCLs have recently been
discovered. An enzyme called palmitoyl-protein thioesterase has been shown
to be insufficiently active in the infantile form of Batten disease (this
condition is now referred to as CLN1). In the late infantile form (CLN2),
a deficiency of an acid protease, an enzyme that hydrolyzes proteins, has
been found as the cause of this condition. A mutated gene has been
identified in juvenile Batten disease (CLN3), but the protein for which
this gene codes has not been identified.
Because vision loss is often an early sign, Batten disease may be first
suspected during an eye exam. An eye doctor can detect a loss of cells
within the eye that occurs in the three childhood forms of NCL. However,
because such cell loss occurs in other eye diseases, the disorder cannot
be diagnosed by this sign alone. Often an eye specialist or other
physician who suspects NCL may refer the child to a neurologist, a doctor
who specializes in diseases of the brain and nervous system.
In order to diagnose NCL, the neurologist needs the patient's medical
history and information from various laboratory tests. Diagnostic tests
used for NCLs include:
- blood or urine tests. These tests can detect abnormalities that may
indicate Batten disease. For example, elevated levels of a chemical called
dolichol are found in the urine of many NCL patients.
- skin or tissue sampling. The doctor can examine a small piece of
tissue under an electron microscope. The powerful magnification of the
microscope helps the doctor spot typical NCL deposits. These deposits are
common in skin cells, especially those from sweat glands.
- electroencephalogram or EEG. An EEG uses special patches placed on the
scalp to record electrical currents inside the brain. This helps doctors
see telltale patterns in the brain's electrical activity that suggest a
patient has seizures.
- electrical studies of the eyes. These tests, which include
visual-evoked responses and electroretinograms, can detect various eye
problems common in childhood NCLs.
- brain scans. Imaging can help doctors look for changes in the brain's
appearance. A commonly used imaging technique is computed tomography, or
CT, which uses x-rays and a computer to create a sophisticated picture of
the brain's tissues and structures. A CT scan may reveal brain areas that
are decaying in NCL patients. Another imaging technique that is becoming
increasingly common is magnetic resonance imaging, or MRI. MRI uses a
combination of magnetic fields and radio waves, instead of radiation, to
create a picture of the brain.
- measurement of enzyme activity. Measurement of the activity of
palmitoyl-protein thioesterase involved in CLN1 and the acid protease
involved in CLN2 in white blood cells or cultured skin fibroblasts can be
used to confirm these diagnoses.
- DNA analysis. If families where the mutation in the gene for CLN3 is
known, DNA analysis can be used to confirm the diagnosis or for the
prenatal diagnosis of this form of Batten disease. When the mutation is
known, DNA analysis can also be used to detect unaffected carriers of this
condition for genetic counseling.
As yet, no specific treatment is known that can halt or reverse the
symptoms of Batten disease or other NCLs. However, seizures can sometimes
be reduced or controlled with anticonvulsant drugs, and other medical
problems can be treated appropriately as they arise. At the same time,
physical and occupational therapy may help patients retain function as
long as possible.
Some reports have described a slowing of the disease in children with
Batten disease who were treated with vitamins C and E and with diets low
in vitamin A. However, these treatments did not prevent the fatal outcome
of the disease.
Support and encouragement can help patients and families cope with the
profound disability and dementia caused by NCLs. Often, support groups
enable affected children, adults, and families to share common concerns
Meanwhile, scientists pursue medical research that could someday yield
an effective treatment.
Within the Federal Government, the focal point for research on Batten
disease and other neurogenetic disorders is the National Institute of
Neurological Disorders and Stroke (NINDS). The NINDS, a part of the
National Institutes of Health, is responsible for supporting and
conducting research on the brain and central nervous system. Through the
work of several scientific teams, the search for the genetic cause of NCLs
is gathering speed.
Other investigators are also working to identify what substances the
lipopigments contain. Although scientists know lipopigment deposits
contain fats and proteins, the exact identity of the many molecules inside
the deposits has been elusive for many years. Scientists have unearthed
potentially important clues. For example one NINDS-supported scientist,
using animal models of NCL, has found that a large portion of this
built-up material is a protein called subunit c. This protein is normally
found inside the cell's mitochondria, small structures that produce the
energy cells need to do their jobs. Scientists are now working to
understand what role this protein may play in NCL, including how this
protein winds up in the wrong location and accumulates inside diseased
cells. Other investigators are also examining deposits to identify the
other molecules they contain.
In addition, research scientists are working with NCL animal models to
improve understanding and treatment of these disorders. One research team,
for example, is testing the usefulness of bone marrow transplantation in a
sheep model, while other investigators are working to develop mouse
models. Mouse models will make it easier for scientists to study the
genetics of these diseases, since mice breed quickly and frequently.
Keeping on Top of Your Condition
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The following voluntary agencies promote research, provide information,
and help affected families.
Batten's Disease Support and Research Association
Columbus, Ohio 43207
Children's Brain Disease Foundation
Parnassus Heights Medical
350 Parnassus Avenue, Suite 900
San Francisco, California
JNCL Research Fund
P.O. Box 766
Mundelein, Illinois 60060
Nathan's Battle Foundation
459 South State Road 135
The Institute for Basic Research, part of the New York state
government, conducts research on NCLs and maintains a registry of affected
Institute for Basic Research
1050 Forest Hill Road
Island, New York 10314