Information on the following diseases can be found in the Related Disorders section of this report:

• Santavouri Disease
• Jansky-Bielschowsky Disease
• Kufs Disease

The symptoms of Batten disease usually become apparent between 5 and 15 years of age. Affected children may develop slowly progressive vision abnormalities, cognitive decline, and behavioral changes.

An early finding in Batten disease is the progressive loss of vision characterized macular degeneration, deterioration of the nerves of the eyes (optic nerves) that transmit impulses from the nerve-rich membrane lining the eyes (retina) to the brain (optic atrophy), and abnormal accumulation of colored (pigmented) material on the retinas (retinitis pigmentosa). Retinitis pigmentosa eventually causes degeneration of the retina leading to progressive loss of vision. Children with Batten disease often lose their sight by the age of 10.

In some children, the first signs of Batten disease are episodes of uncontrolled electrical disturbances in the brain (seizures) and the loss of previously acquired physical and mental abilities (developmental regression). As affected individuals age, seizures worsen, signs of dementia become apparent, and motor abnormalities similar to those seen in Parkinson's disease develop. During this period, behavioral and personality changes often occur including mood disturbances, anxiety, psychotic states (such as explosive, unprovoked laughing and/or crying) and hallucinations. Speech disturbances such as stuttering may also occur.

Eventually, usually during the late teens or twenties additional abnormalities develop including sudden involuntary muscle contractions (myoclonus), muscle spasms (spasticity) that result in slow, stiff movements of the legs, weakness or paralysis of all four limbs (quadriparesis), and sleep disturbances. In most cases, progressive neurological and mental degeneration leaves affected individuals bedridden and unable to communicate easily and eventually results in life-threatening complications by the twenties.

Batten disease is inherited as an autosomal recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

Investigators have determined that Batten disease occurs because of disruptions or changes (mutations) of the CLN3 gene located on the short arm (p) of chromosome 16 (16p12.1). The function of the protein encoded by this gene is not yet understood. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 16p12.1" refers to band 12.1 on the short arm of chromosome 16. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Researchers suspect that Batten disease is caused by alterations within the cell so that the body is unable to break down substances such as fats, and their associated sugars and proteins in the normal way. Some of these fats, sugars, and proteins then appear to form the lipopigments that accumulate in nerve and other tissue causing the symptoms associated with this disorder. Although these substances accumulate in most cells, brain cells are affected first.

Batten disease affects males and females in equal numbers. In the United States, Batten disease along with the other forms of neuronal ceroid lipofuscinoses, occurs in approximately three in 100,000 births. It can occur with greater frequency in families of Northern European Scandinavian ancestry; in particular, those of Swedish heritage. It is thought to occur in one in 25,000 infants in northern Europe. The symptoms of Batten disease usually begins between five and seven years of age. Batten disease is one of the most common neurodegenerative disorders affecting children.

Symptoms of the following disorders can be similar to those of Batten disease. Comparisons may be useful for a differential diagnosis.

Santavuori disease, an extremely rare genetic disorder, is the infantile form of neuronal ceroid lipofuscinosis (NCL). In most cases, infants with Santavuori disease appear to develop normally until approximately nine to 19 months of age, but some children do not become ill until later because their genetic defect does not completely abolish the function of the gene that normally causes INCL and their disease can be very like JNCL. Affected infants may begin to exhibit a delay in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor retardation). In addition, they may begin to lose previously acquired physical and mental abilities (developmental regression). They may experience a variety of symptoms including episodes of uncontrolled electrical disturbances in the brain (seizures), impaired ability to coordinate voluntary movements (cerebellar ataxia), abnormally diminished muscle tone (hypotonia), and repeated, brief, shock-like muscle spasms of the arms, legs, or entire body (myoclonic seizures). Affected infants may also experience progressive visual impairment due to deterioration of the nerves of the eyes (optic nerves) that transmit impulses from the nerve-rich membranes lining the eyes (retina) to the brain (optic atrophy). Neurological impairment continues to progress and may be characterized by an inability to move voluntarily (immobility); sudden involuntary muscle spasms (spasticity); and lack of response to stimuli in the environment. Life-threatening complications may develop by the end of the first decade. Santavuori disease is inherited as an autosomal recessive trait. (For more information on this disorder, choose "Santavuori" as your search term in the Rare Disease Database.)

Jansky-Bielschowsky disease is the late infantile form of neuronal ceroid lipofuscinosis (NCL). The onset of symptoms associated with the disorder typically begins between the ages of two to four years of age, but some children do not become ill until an older age. Until that time, children with the disorder appear to develop normally or may exhibit slight delays in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor retardation). Between two to four years of age, they may then begin to experience seizure episodes characterized by sudden breaks in action or thought, twitching of certain facial muscles, and/or spasms of the neck and/or arms (petit mal seizures) and/or episodes characterized by loss of consciousness occurring in association with muscle contractions (grand-mal seizures). Affected children also begin to demonstrate repeated, brief, shock-like muscle spasms of the arms, legs, or entire body (myoclonic seizures); impaired ability to coordinate voluntary movement (ataxia); abnormally diminished muscle tone (hypotonia) with unusually exaggerated reflexes; gradual intellectual deterioration; and/or, in some cases, visual failure due to retinal degeneration. In addition, a variant of Jansky-Bielschowsky disease has been identified in individuals of Finnish descent. In this variant form, symptoms tend to appear later, at approximately five to seven years of age, and tend to progress more slowly than in the classic form of the disorder. Jansky-Bielschowsky disease is inherited as autosomal recessive traits. (For more information on this disorder, choose "Jansky-Bielschowsky" as your search term in the Rare Disease Database.)

Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body's cells as a result of enzyme deficiencies. There are nearly 50 of these disorders altogether, and they may affect different parts of the body, including the skeleton, brain, skin, heart, and central nervous system. New lysosomal storage disorders continue to be identified. While clinical trials are in progress on possible treatments for some of these diseases, there is currently no approved treatment for many lysosomal storage diseases. (For more information on this disorder, choose "lysosomal storage disease" as your search term in the Rare Disease Database.)

Diagnosis
A diagnosis of Batten disease may be made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic physical findings, and a variety of specialized tests including the microscopic examination (i.e., electron microscopy) and study of the chemical components (histochemical examination) of samples of tissue (biopsy), usually from the skin. The study of such tissue samples reveals abnormal accumulations of deposits (i.e., pigmented lipids [lipopigments] ceroid and lipofuscin) in membrane-bound cavities within the body (cytoplasm) of cells (inclusion bodies). In JNCL these have a characteristic appearance rather like fingerprints. Similar deposits may also be present in other tissues and cells of the body (e.g., certain white blood cells [lymphocytes].

In addition, in children with Batten disease, electroretinography (ERG), a special instrument that measures the retina's electrical response to light stimulation, may reveal lack of response when the eye is stimulated by light (visually evoked potential [VEP]), confirming progressive retinal pigmentary degeneration and/or optic nerve abnormalities (e.g., optic atrophy). Unique to this type of NCL is the presence of vacuoles in lymphocytes, easily visible at the trailing edges of blood films.

Almost all children affected with JNCL carry a 1kb intragenic deletion that can be detected using a simple DNA-based test.

Treatment
The treatment of Batten disease is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat neurological disorders (neurologists), eye specialists (ophthalmologists), physical therapists, psychiatrists, and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.

Specific therapies for Batten disease are symptomatic and supportive. In some cases, treatment with anticonvulsant drugs such as valproate and lamotrigine may help prevent, reduce, or control various types of seizures associated with Batten disease. Medications may also be used to help psychiatric symptoms such as hallucinations.

Early intervention is important to ensure that children with Batten disease reach their potential. Special services that may be beneficial to affected children may include special remedial education, special social support, and other medical, social, and/or vocational services. Genetic counseling may be of benefit for affected individuals and their families.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Patients are being recruited (2005) for a Phase II clinical trial of the drug Cystagon for the treatment of infantile neuronal ceroid lipofuscinosis. This study is sponsored by the National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH). For information, go to www.clinicaltrials.gov or contact the NIH sources listed above.

A California company, StemCells Inc., is in communication (2005) with the U.S. Food and Drug Administration (FDA) regarding a proposed Phase I trial of the company's neural cell-therapy product, HuCNS, in treating Batten disease.

TEXTBOOKS
Goebel HH, Mole SE, Lake BD. The neuronal ceroid lipofuscinoses (Batten disease). 1st edition. IOS Press. 1998. 198 pp. 2nd edition due: 2007.

Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 17th ed. Elsevier Saunders. Philadelphia, PA; 2005:2032.

Dyken PR. Batten Disease. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:516-7.

Rimoin D, Connor JM, Pyeritz RP, Korf BR, eds. Emory and Rimoin's Principles and Practice of Medical Genetics. 4th ed. Churchill Livingstone. New York, NY; 2002:3057-9.

Lyon G, Adams RD, Kolodny EH, eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. McGraw-Hill Companies. New York, NY; 1996:.

Menkes JH, Pine Jr JW, et al., eds. Textbook of Child Neurology. 5th ed. Williams & Wilkins. Baltimore, MD; 1995:111-6.

JOURNAL ARTICLES
Mole SE, Williams RE, Goebel HH. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid liposfuscinoses. Neurogenetics. 2005;6:107-26.

Mole SE, Mitchison HM, Munroe PB. Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5. Hum Mutat. 1999;14:199-215.

Boustany RM. Neurology of the neuronal ceroid-lipofuscinoses: late infantile and juvenile types. Am J Med Genet. 1992;533-5.

Gardiner M, Sanford A, Deadman M, et al. Batten disease (Spielmeyer-Sjorgren disease, juvenile onset neuronal ceroid-lipofuscinosis) gene (CLN3) maps to human chromosome 16. Genomics. 1990;8:387-90.

Eiberg H, Gardiner RM, Mohr J. Batten disease (Spielmeyer-Sjogren disease) and haptoglobins (HP): indication of linkage and assignment to chromosome 16. Clin Genet. 1989;36:217-8.

ON THE INTERNET
Mole SE. NCL Resource Site--A Gateway for Batten Disease. Available at: http://www.ucl.ac.uk/ncl. Accessed one: August 29, 2006.

Chang CH. Neuronal Ceroid Lipofuscinoses. Emedicine Journal, April 24, 2006. Available at: http://www.emedicine.com/neuro/topic498.htm Accessed on: August 18, 2006.

Wisniewski KE. Updated:5/17/2006. Neuronal Ceroid-Lipofuscinoses. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2003. Available at http://www.genetests.org.

National Institute of Neurological Disorders and Stoke. Batten Disease Fact Sheet. January 23, 2006. Available at: http://www.ninds.nih.gov/disorders/batten/detail_batten.htm Accessed On: August 18, 2006.

Kohlschutter A. Neuronal Ceroid Lipofuscinoses. Orphanet encyclopedia, January 2004. Available at: http://www.orpha.net/data/patho/GB/uk-CLN.pdf Accessed on: August 18, 2006.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:204200; Last Update:03/24/2006. Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=204200 Accessed on: August 18, 2006.