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, it has now become the term to encompass all forms of NCL.

The forms of NCL are classified by age of onset have the same basic cause, progression and outcome but are all genetically different Over time, affected children suffer mental impairment, worsening seizures, and progressive loss of sight and motor skills. Eventually, children with Batten Disease/NCL become blind, bedridden, and unable to communicate and it is presently always fatal. Batten Disease is not contagious or, at this time, preventable.

What are the forms of NCL/Batten’s Disease?

There are four main types of NCL, including two forms that begin earlier in childhood and a very rare form that strikes adults. The symptoms are similar 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. Initial signs of this disorder include delayed psychomotor development with progressive deterioration, other motor disorders, or seizures. The infantile form has the most rapid progression and children live into their mid childhood years.

Late Infantile NCL (Jansky-Bielschowsky disease): begins between ages 2 and 4. The typical early signs are loss of muscle coordination (ataxia) and seizures along with progressive mental deterioration. This form progresses rapidly and ends in death between ages 8 and 12.

Juvenile NCL (Batten Disease): begins between the ages of 5 and 8 years of age. The typical early signs are progressive vision loss, seizures, ataxia or clumsiness. This form progresses less rapidly and ends in death in the late teens or early 20s, although some may live into their 30s.

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.

There are six additional diseases included in the Batten Disease/NCL group:

• Finnish Late Infantile - identified in Finland.
• Variant Late Infantile - identified in Costa Rica, South America, Portugal and other nations.
• Turkish Late Infantile - identified in Turkey.
• Northern Epilepsy/ERMP - Epilepsy with Mental Retardation - identified in Finland.
• Variant Juvenile - identified in Germany and USA.
• Congenital/CTSD - identified in Europe

How many people have these disorders?

Batten Disease/NCL is relatively rare, occurring in an estimated 2 to 4 of every 100,000 births in the United States. The diseases have been identified worldwide. Although NCLs are classified as rare diseases, they often strike more than one person in families that carry the defective gene.

How are NCL’s 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 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. 

Adult NCL may be inherited as an autosomal recessive (Kufs) or, less often, as an autosomal dominant (Parrys) 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.

CAUSES/DIAGNOSIS

What causes these diseases?Symptoms of Batten Disease/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 (or comas) and are called curvilinear bodies, others look like fingerprints and are called fingerprint inclusion bodies and still others resemble gravel (or sand) and are called granual osmophilic deposits (grods). 

These deposits are what doctors look for when they examine a skin sample to diagnose Batten Disease. The diseases cause death of neurons (specific cells found in the brain, retina and central nervous system). The reason for neuron death is still not known.

How are these disorders diagnosed?

Because vision loss is often an early sign, Batten Disease/NCL 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 Batten Disease/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 Batten Disease/NCL may refer the child to a neurologist, a doctor who specializes in disease of the brain and nervous system. In order to diagnose Batten Disease/NCL, the neurologist needs the patient's medical history and information from various laboratory tests. Diagnostic tests used for Batten Disease/NCLs include: 

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 found in many different tissues, including skin, muscle, conjunctiva, rectal and others. Blood can also be used. 

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 (VER) and electro-retinagrams (ERG), can detect various eye problems common in childhood Batten Disease/NCLs. 

Brain scans. Imaging can help doctors look for changes in the brain's appearance. The most commonly used imaging technique is computed tomography (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. 

Enzyme assay. A recent development in diagnosis of Batten Disease/NCL is the use of enzyme assays that look for specific missing lysosomal enzymes for Infantile and Late Infantile only. This is a quick and easy diagnostic test. 

Genetic/DNA testingEach 'form' of Batten disease is the result of a different gene. Genes for eight or the ten forms have been identified. Testing for these is avaialable for diagnosis as well as carrier and prenatal status.


TREATMENT/RESEARCH

Is there any treatment?

As yet, no specific treatment is known that can halt or reverse the symptoms of Batten Disease/NCL. However, seizures can 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 children and families cope with the profound disability and losses caused by NCLs. The Batten Disease Support and Research Association enables affected children, adults, and families to share common concerns and experiences. Meanwhile, scientists pursue medical research that will 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 (NIH), is responsible for supporting and conducting research on the brain and central nervous system. The Batten Disease Support and Research Association and the Children's Brain Diseases Foundation also provide financial assistance for research. 

Through the work of several scientific teams, the search for the genetic cause of NCLs is gathering speed. In September 1995, The International Batten Disease Consortium announced the identificatiion of the gene for the juvenile form of Batten Disease. The specific gene, CLN3, located on Chromosome 16, has a deletion or piece missing. This gene accounts for 73% of all cases of Juvenile Batten Disease. The rest are the result of other defects of the same gene. 

Also, in 1995, scientists in Finland announced the identification of the gene responsible for the infantile form of Batten Disease. The gene, CLN1, is located on Chromosome 1. 

In September 1997, scientists at the Robert Woos Johnson Medical School and the Institute for Basic Research, NY, announced the identification of the gene for the "classic" Late Infantile form of Batten Disease/NCL. The gene, CLN2, is located on chromosome 11. 

Scientists have also identified the genes responsible for Finnish Late Infantile (CLN5), variant Late Infantile (CLN6), EPMR (CLN8) and Congenital/CTSD (CLN10). Research also continues toward identification of the gene for the adult form of Batten Disease/NCL, also known as Kufs Disease. 

Identification of the specific genes for Infantile, Late Infantile, Variant Late Infantile and Juvenile Batten Disease/NCL has led to the development of DNA diagnostics, carrier and prenatal tests. 

Scientists have discovered that the Infantile and Late Infantile diseases are missing key lysosomal enzymes, i.e. Palmitoyl Protein Thioesterase 1 (PPT1) for Infantile and Tripeptidyl Peptidase 1 (TPP1) for Late Infantile. Knowing that these enzymes are missing is now leading to the development of gene replacement and stem cell transplantation therapies. 

Recent studies have shown a link between the Juvenile form and the body's autoimmune system. Although this link is not yet fully understood, it may eventually lead to a treatment. 

Currently there is a drug trials underway for Infantile Batten Disease/NCL. This trials is using a drug by the name of Cystagons. For additional information regarding this trial, contact BDSRA at 1-800-448-4570.