Batten Disease

What is Batten disease?

     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.  Batten disease is not contagious or, at this time,

What are the other 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 different rates.

     - 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 years longer.

     - 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 Party'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.

How many people have these disorders?

     Batten disease and other forms of NCL are relatively rare,
     occurring in an estimated 2 to 4 of every 1 00,000 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 gene.

How are NCLs inherited?

     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.  There is no test yet available to identify
     carriers of Batten disease or other forms of NCL.

     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.

What causes these diseases?

     Symptoms of Batten disease and other NCLs are linked to a
     buildup of substances called 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 causing NCLs have not been
     identified.  Some scientists suspect these abnormal deposits
     result from a shortage of enzymes normally responsible for
     the breakdown of lipopigments.  According to this theory,
     diseased cells  produce inadequate amounts of enzymes or
     manufacture defective enzymes that function poorly.  As a
     result, the cells cannot process enough of the lipopigments
     that occur within them, and the lipopigments accumulate. 
     However, scientists have not pinpointed what specific
     enzymes are at fault or determined how the stored
     lipopigments damage nerve cells.

     Other scientists believe that abnormal lipopigment buildup
     may result from a glitch in their production or processing. 
     For example, diseased cells could be producing too much of a
     normally needed lipoprotein.

How are these disorders diagnosed?

     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

     - 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.  The most 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.  A second imaging
     technique that is 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.

Is there any treatment?

     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 and

     Meanwhile, scientists pursue medical research that could
     someday yield an effective treatment.

What research is being done?

     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.  Previous
     research has uncovered a link between juvenile NCL, or
     Batten disease, and certain markers on chromosome 16.  With
     the help of affected families, NINDS-supported scientists
     are now conducting research to confirm this link and narrow
     the search for the culprit gene.  Pinpointing the gene will
     enable physicians to provide patients with earlier and more
     accurate diagnosis and to identify carriers of the gene.  It
     may also help us understand what body processes go awry in
     Batten disease and thereby open the door to new treatments.

     Some scientists are investigating the theory that children
     with Batten disease have a shortage of a key body enzyme. 
     Investigators are searching for enzymes that might be
     scarce, defective, or completely missing.  One team of
     scientists, for example, is testing the theory that a
     specific enzyme, called phospholipase A1, is  deficient in
     people with Batten disease.  Such studies could also prove
     useful in better diagnosis of patients. In addition,
     identifying an enzyme at fault might make it possible to
     treat affected children with natural or synthetic enzymes
     that would counter-act the shortage and clear away stored
     material. In fact, NINDS scientists have used this approach
     to successfully treat another storage disorder known as
     Gaucher's disease.

     At the same time, other investigators are 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.  Recently,
     however, 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 a new mouse
     model. If successfully developed, mouse models will make it
     easier for scientists to study the genetics of these
     diseases, since mice breed quickly and frequently.

How can I help research?

     The NINDS and the National Institute of Mental Health
     support two national human brain specimen banks.  These
     banks supply investigators around the world with tissue from 
     patients with neurological and psychiatric diseases.  Both
     banks need brain tissue from Batten disease patients to
     enable scientists to study this disorder more intensely. 
     Prospective donors or their families should contact:

     Dr. Wallace W. Tourtellotte, Director
     Human Neurospecimen Bank
     VA Wadsworth Medical Center
     Wilshire and Sawtelle Blvds.
     Los Angeles, California 90073
     (310) 824-4307

     Dr. Edward D. Bird, Director
     Brain Tissue Bank, Mailman Research Center
     McLean Hospital
     115 Mill Street
     Belmont, Massachusetts 02178
     1-800-BRAIN-BANK (27246-2265)
     (617) 855-2400

Where can I find more information?

     The following voluntary agencies promote research, provide
     information, and help affected families.

     Children's Brain Disease Foundation for Research
     350 Parnassus Avenue, Suite 900
     San Francisco, California 94117
     (415) 566-5402

     Batten's Disease Support and Research Association
     2600 Parsons Avenue
     Columbus, Ohio 43207
     (800) 448-4570

     The Institute for Basic Research in Developmental
     Disabilities, part of the New York state government,
     conducts research on NCLs and maintains a registry of
     affected families.

     Institute for Basic Research in Developmental Disabilities
     1050 Forest Hill Road
     Staten Island, New York 10314
     (718) 494-0600

     NINDS information
     For more information on research programs of the NINDS,
     contact:  Office of Scientific and Health Reports
     Neurological Institute
     P.O. Box 5801
     Bethesda, Maryland 20824
     (301) 496-5751
     (800) 352-9424

Prepared by:
Office of Scientific and Health Reports National Institute of Neurological Disorders and Stroke National Institutes of Health
June 1992