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| Batten Disease General Information | |||
| What
is Batten Disease?
What is the history of Batten Disease? What are the other forms of NCL? How many people have these disorders? How are NCLs inherited? What causes these diseases? How are these disorders diagnosed? Is there any treatment? What research is being done? How can I help research? Where can I find more information? |
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What is Batten Disease?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 presently is always fatal. Batten Disease is not contagious or, at this time, preventable. History of Neuronal Ceroid Lipofuscinosis The first probable instances of this condition were reported in 1826 in a Norwegian medical journal by Dr. Christian Stengel, who described 4 affected siblings in an small mining community in Norway. Although no pathological studies were performed on these children the clinical descriptions are so succinct that the diagnosis of the Spielmeyer-Sjogren (juvenile) type is fully justified. More fundamental observations were reported by F. E. Batten in 1903, and by Vogt in 1905, who performed extensive clinicopathological studies on several families. Retrospectively, these papers disclose that the authors grouped together different types of the syndrome. Furthermore Batten, at least for some time, insisted that the condition that he described was distinctly different from Tay-Sachs Disease, the prototype of a neuronal lysosomal disorder now identified as GM2-Gangliosidosis type A. Around the same time, Spielmeyer reported detailed studies on three siblings, suffering from the Spielmeyer-Sjogren (juvenile) type, which led him to the very firm statement that this malady is not related to Tay-Sachs Disease. Subsequently, however, the pathomorphological studies of Schaffer made these authors change their minds to the extent that they reclassified their respective observations as variants of Tay-Sachs Disease, which caused confusion lasting about 50 years.. In 1913-14, M. Bielschowsky delineated the Late Infantile form of NCL. However, all forms were still thought to belong in the group of "familial amaurotic idiocies", of which, Tay-Sachs was the prototype. In 1931, the Swedish psychiatrist and geneticist, Torben Sjogren, presented 115 cases with extensive clinical and genetic documentation and came to the conclusion that the disease which we now call the Spielmeyer-Sjogren (juvenile) type is genetically separate from Tay Sachs. Departing from the careful morophological observations of Spielmeyer, Hurst, and Sjovall and Ericsson, Zeman and Alpert made a determined effort to document the previously suggested pigmentary nature of the neuronal deposits in certain types of storage disorders. Simultaneously, Terry and Korey and Svennerholm demonstrated a specific ultrastructure and biochemestry for Tay Sachs Disease, and these developments led to the distinct identification and also separation of the NCLs from Tay Sachs Disease by Zeman and Donahue. At that time, it was proposed that the Late Infantile (Jansky-Bielschowsky), the Juvenile (Spielmeyer-Vogt), and the adult form (Kufs) were quite different from Tay-Sachs Disease with respect to chemical pathology and ultrastructure and also different from other forms of sphingolipidoses. Subsequently, it was shown by Santavuori and Haltia that an infantile form of NCL exists, which Zeman and Dyken had included with the Jansky Bielschowsky type. What are the forms of NCL/Batten 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.
There are four additional
diseases included in the Batten Disease/NCL group: 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 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 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. 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:
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 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 gene responsible for Finnish Late Infantile (CLN5), variant Late Infantile (CLN6) and EPMR (CLN8). 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 are two drug
trials underway for Infantile Batten Disease/NCL. Both trials are using
a drug by the name of Cystagon. For additional information regarding this
trial, contact BDSRA at 1-800-448-4570. The hope of the future lies in research. Scientists need blood and tissue samples in order to develop cell lines for current and future investigations. Cell lines of persons with Batten Disease and their families are grown and maintained in cell banks located at Institute for Basic Research in Staten Island, NY and at Massachusetts General Hospital. Post mortem brain and other tissue is banked in the National Neurological Research Specimen Bank in Los Angeles. These "banks" provide samples for research worldwide. To donate blood or tissue contact the Batten Disease Support and Research Association at 1-800-448-4570 or e-mail: bdsra1@bdsra.org. As everyone knows, scientific research of any kind is driven by funding. BDSRA provides funding to keep research moving forward. Financial assistance for scientific investigations into the cause and future treatment of Batten Disease/NCL is always needed. Persons interested in aiding research may also call BDSRA at 1-800-448-4570 or e-mail: bdsra1@bdsra.org. Where can I find more information?Batten
Disease Support and Research Association Children's
Brain Disease Foundation for Research
Institute
for Basic Research in Developmental Disabilities
For more information on research
programs of the NINDS, contact: |
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Last
Updated/Reviewed
9/27/07
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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.