Batten Disease 

and other Neuronal 

Ceroid Lipofucinoses 

U.S. DEPARTMENT OF HEALTH 

AND HUMAN SERVICES 

Public Health Service 

National Institutes of Health 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Batten Disease 

and other Neuronal Ceroid Lipofucinoses 

What is Batten disease? 

Batten disease is a fatal, inherited disorder of the nervous system that typically 

begins in childhood. Early symptoms of this 

disorder usually appear between the ages 

of 5 and 10 years, 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-SjögrenBatten disease, it is the most common form 

of a group of disorders called the neuronal 

ceroid lipofuscinoses, or NCLs. Although 

Batten disease originally referred specifically 

to the juvenile form of NCL (JNCL), the 

term Batten disease is increasingly used by 

pediatricians to describe all forms of NCL. 

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What are the other forms of NCL? 

There are four other main types of NCL, including three forms that begin earlier 

in childhood and a very rare form that strikes 

adults. The symptoms of these childhood 

types are similar to those caused by Batten 

disease, but they become apparent at different ages and progress at different rates. 

•	 Congenital NCL is a very rare and severe 

form of NCL. Babies have abnormally 

small heads (microcephaly) and seizures, 

and die soon after birth. 

•	 Infantile NCL (INCL or SantavuoriHaltia disease) begins between about 

ages 6 months and 2 years and progresses 

rapidly. Affected children fail to thrive 

and have microcephaly. Also typical are 

short, sharp muscle contractions called 

myoclonic jerks. These children usually 

die before age 5, although some have 

survived in a vegetative state a few 

years longer. 

•	 Late infantile NCL (LINCL, or JanskyBielschowsky 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 (also known as Kufs disease, 

Parry’s disease, and ANCL) generally 

begins before age 40, causes milder 

symptoms that progress slowly, and does 

not cause blindness. Although age of 

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death varies among affected individuals, 

this form does shorten life expectancy. 

There are also “variant” forms of late-infantile 

NCL (vLINCL) that do not precisely conform 

to classical late-infantile NCL. 

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 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. 

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. Because 

the mutated genes that are involved in certain 

forms of Batten disease are known, carrier 

detection is possible in some instances. 

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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 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. The 

substances are found inside a part of cells 

called lysosomes. Lysosomes are responsible 

for getting rid of things that become damaged 

or are no longer needed and must be cleared 

from inside the cell. The accumulated lipopigments in Batten disease and the other NCLs 

form 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 specific appearance of 

the lipopigment deposits can be useful in 

guiding further diagnostic tests that may 

identify the specific gene defect. 

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To date, eight genes have been linked to the 

varying forms of NCL. Mutations of other 

genes in NCL are likely since some individuals 

do not have mutations in any of the known 

genes. More than one gene may be associated 

with a particular form of NCL. The known 

NCL genes are: 

CLN1, also known as PPT1, encodes an 

enzyme called palmitoyl-protein thioesterase 

1 that is insufficiently active in Infantile NCL. 

CLN 2, or TPP1, produces an enzyme called 

tripeptidyl peptidase 1—an acid protease 

that degrades proteins. The enzyme is insufficiently active in Late Infantile NCL (also 

referred to as CLN2). 

CLN3 mutation is the major cause of Juvenile 

NCL. The gene codes for a protein called 

CLN3 or battenin, which is found in the 

membranes of the cell (most predominantly 

in lysosomes and in related structures called 

endosomes). The protein’s function is currently unknown. 

CLN5, which causes variant Late Infantile 

NCL (vLINCL, also referred to as CLN5), 

produces a lysosomal protein called CLN5, 

whose function has not been identified. 

CLN6, which also causes Late Infantile NCL, 

encodes a protein called CLN6 or linclin. The 

protein is found in the membranes of the cell 

(most predominantly in a structure called the 

endoplasmic reticulum). Its function has not 

been identified. 

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MFSD8, seen in variant Late Infantile NCL 

(also referred to as CLN7), encodes the 

MFSD8 protein that is a member of a 

protein family called the major facilitator 

superfamily. This superfamily is involved 

with transporting substances across the cell 

membranes. The precise function of MFSD8 

has not been identified. 

CLN8 causes progressive epilepsy with mental 

retardation. The gene encodes a protein also 

called CLN8, which is found in the membranes 

of the cell—most predominantly in the endoplasmic reticulum. The protein’s function 

has not been identified. 

CTSD, involved with Congenital NCL (also 

referred to as CLN10), encodes cathepsin D, 

a lysosomal enzyme that breaks apart other 

proteins. A deficiency of cathepsin D causes 

the disorder. 

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 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 

for additional testing. 

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In order to diagnose NCL, the neurologist 

needs the individual’s medical and family 

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 individuals with NCL. 

The presence of vacuolated lymphocytes— 

white blood cells that contain holes or 

cavities (observed by microscopic analysis 

of blood smears)—when combined with 

other findings that indicate NCL, is suggestive for the juvenile form caused by 

CLN3 mutations. 

•	 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 an individual 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. 

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•	 diagnostic imaging using computed 

tomography (CT) or magnetic resonance 

imaging (MRI). Diagnostic imaging can 

help doctors look for changes in the brain’s 

appearance. CT uses x-rays and a computer 

to create a sophisticated picture of the 

brain’s tissues and structures, and may 

reveal brain areas that are decaying, or 

“atrophic,” in persons with NCL. 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, the acid 

protease involved in CLN2, and, though 

more rare, cathepsin D activity involved 

in CLN10, in white blood cells or cultured 

skin fibroblasts (cells that strengthen 

skin and give it elasticity) can be used 

to confirm or rule out 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. If 

a family mutation has not previously been 

identified or if the common mutations are 

not present, recent molecular advances 

have made it possible to sequence all of the 

known NCL genes, increasing the chances 

of finding the responsible mutation(s). 

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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 experiences. 

Meanwhile, scientists pursue medical 

research that could someday yield an 

effective treatment. 

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What research is being done? 

T he National Institute of Neurological Disorders and Stroke, a part of the 

National Institutes of Health, is the 

Federal government’s leading supporter 

of biomedical research on the brain and 

central nervous system. As part of its 

mission, the NINDS conducts research and 

supports studies through grants to major 

medical institutions across the country. 

Through the work of several scientific 

teams, the search for the molecular basis 

of the NCLs is gathering speed. 

Studying the lipopigment deposits that 

contain fats and proteins, one NINDSsupported scientist, using animal models 

of NCL, 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 

accumulates inside diseased cell and 

whether its accumulation—or the accumulation of other components in the storage 

material—is harmful to the cell. An important aspect of these studies is looking at 

how the different gene mutations lead to 

the lipoprotein deposits, which may involve 

the same processes. 

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In addition, research scientists are working 

with NCL animal models to improve understanding and treatment of these disorders. 

These include naturally occurring sheep 

and dog models, and genetically engineered 

mouse models. Simpler models in lower 

organisms (such as yeast, zebrafish, and 

the fruit fly) are useful tools that are 

being implemented by scientists to study 

the function of the NCL proteins, most of 

which remain unknown. Research suggests 

that many of the NCL genes have conserved 

functions in the lower organisms; in other 

words, they work the same way in yeast, 

fly, or zebrafish cells as they do in humans. 

Because mice and lower organisms breed 

or propagate quickly and can be genetically manipulated, their use can speed 

NCL research. 

More recently, advances in human cell 

research will assist the translation of findings in the model organisms to individuals 

with NCL disorders. Skin or other cell types 

taken from those with an NCL disorder can 

now be manipulated in the laboratory to 

become “pluripotent,” meaning they can 

made into cells that have the potential to 

become any cell type—including brain 

cells. This process—known as cellular 

reprogramming—is used to establish 

patient-derived induced pluripotent stem 

cells (iPS cells). 

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Although no therapies at currently available 

for NCL disorders, a number of NINDSfunded science teams are working toward 

developing therapies and identifying therapy 

targets for NCL. The approaches undertaken 

by scientists include: 

•	 gene therapy (for example, in CLN1 

and CLN2) 

•	 enzyme replacement therapy (CLN1 

and CLN2) 

•	 stem cell therapy 

•	 identification of the normal protein 

functions that are lost as a result of 

the gene mutations 

•	 testing candidate drugs that modify 

known disease abnormalities (for 

example, immune suppression to 

eliminate the observed autoimmunity 

in JNCL/CLN3); and 

•	 screening to identify drugs or other 

factors that normalize cellular abnormalities in the NCL disease models. 

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How can I help research? 

T he NINDS supports 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: 

Human Brain and Spinal Fluid 

Resource Center 

Neurological Research (127A) 

W. Los Angeles Healthcare Center 

11301 Wilshire Boulevard 

Building 212, Room 16 

Los Angeles, CA 90073 

310-268-3536 

24-hour pager: 310-636-5199 

www.loni.ucla.edu/uclabrainbank 

Harvard Brain Tissue Resource Center 

McLean Hospital 

115 Mill Street 

Belmont, MA 02478 

617-855-2400 

800-BRAIN-BANK (800-272-4622) 

www.brainbank.mclean.org 

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Two organizations not funded by the 

NINDS also provide research scientists 

with nervous system tissue from individuals 

with neurological disorders. Interested 

donors should write or call: 

National Disease Research Interchange 

8 Penn Center, 15th floor 

1628 JFK Boulevard 

Philadelphia, PA 19103 

215-557-7361 

800-222-NDRI (6374) 

www.ndriresource.org 

University of Miami 

Miller School of Medicine 

Brain Endowment Bank 

1501 NW 9th Avenue, Room 4013 (D4-5) 

Miami, FL 33136 

305-243-6219 

800-UM-BRAIN (862-7246) 

http://brainbank.med.miami.edu 

Where can I get more information? 

For more information on neurological disorders or research programs funded 

by the National Institute of Neurological 

Disorders and Stroke, contact the Institute’s 

Brain Resources and Information Network 

(BRAIN) at: 

BRAIN 

P.O. Box 5801 

Bethesda, MD 20824 

800-352-9424 

www.ninds.nih.gov 

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Information on Batten disease is also available from the following organizations: 

Batten Disease Support and 

Research Association 

120 Humphries Drive, Suite 2 

Reynoldsburg, OH 43068 

740-927-4298 

800-448-4570 

www.bdsra.org 

Children’s Brain Disease Foundation 

[A Batten Disease Resource] 

Parnassus Heights Medical Building 

Suite 900 

350 Parnassus Avenue 

San Francisco, CA 94117 

415-665-3003 

Nathan’s Battle Foundation 

[For Batten Disease Research] 

459 South State Road 135 

Greenwood, IN 46142 

317-888-7396 

www.nathansbattle.com 

Hide and Seek Foundation for 

Lysosomal Storage Disease Research 

6475 East Pacific Coastal Highway 

Suite 466 

Long Beach CA 90803 

877-621-1122 

www.hideandseek.org 

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Prepared by: 

Office of Communications and Public Liaison 

National Institute of Neurological Disorders and Stroke 

National Institutes of Health 

Department of Health and Human Services 

Bethesda, Maryland 20892 2540 

NIH Publication No. 11 2790 May 2011