Carling and Colton have both been diagnosed with Late Infantile Neuronal Ceroid Lipofuscinosis (NCL). It is one of about ten variations of NCL, which are often grouped together and referred to as Batten Disease.

Late Infantile NCL is a degenerative neurological disorder. It is genetic and both parents must be carriers for a child to develop NCL. Over time, affected children suffer mental impairment, worsening seizures, and progressive loss of sight and motor skills. Eventually, children with NCL become blind, bedridden, and unable to communicate. Until recently, there has been no treatment or cure for NCL. Now research is moving towards positive therapies and solutions for some of the various forms. (see BDSRA website:

What are the forms of NCL?

There are four main types of NCL, all of which have the symptoms described above. Each form of NCL is named for the age at which the person is normally affected:

Infantile NCL (Santavuori-Haltia disease) begins between about 6 months and 2 years of age and has a life expectancy of 6 to 10 years.

Late Infantile NCL (Jansky-Bielschowsky disease) begins between the ages of 2 and 4. Its average life expectancy is 9 to 11 years.

Juvenile NCL (Batten Disease) begins between the ages of 5 and 8 years of age. Those affected by it usually live into their late teens or early twenties, although some have survived into their thirties.

Adult NCL (Kufs or Parry’s Disease) generally begins before the age of 40. While the life expectancy varies, the disorder does shorten life expectancy.

How many people have these disorders?

NCL is relatively rare, occurring in an estimated 2 to 4 of every 100,000 births in North America. The disorders have been identified worldwide, although they appear to be more common in Newfoundland, and in Finland, Sweden and other parts of northern Europe. 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?

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 a 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.

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.

If you are directly related to an NCL family:

For family members wanting to know if they are carriers… ask the parent of the NCL child you are related to what their genetic “change” is… and bring this to your physician who will tell you the nearest facility which will do the genetic blood testing. A charge for the blood test may apply depending on your location and situation. (this is not a test usually done in regular/mainstream labs)

They generally only test if you are considering having children or are pregnant, and are immediate family – siblings or cousins to the NCL parents. If a parent is not a carrier, none of their children will be, unless the other parent happens to have another strain of this rare disorder. The good news is that if you know what you are looking for, only a blood test is needed to find out if you are a carrier.

Knowing you are a carrier does NOT mean you will develop NCL or pass it along to your children. It is a very rare disorder. Both parents must be carriers, for a one in 4 chance their child will develop NCL. If a parent is a carrier, then testing (more involved, but also with bloodwork) can be done on the spouse, and if the female is pregnant, on the child if both parents are carriers.

For Wilson/Gill family members being tested to see if you are a carrier… a blood test can be done at a specialized facility (Sick Kids’ hospital in Canada) which will identify if you are a carrier. If related to Diane, have them check Chromosome 11 for Intron 5: G556C. If you are related to John, have them check if Exon 8 has a T to a C change at positon #4383.

What causes these disorders?

Symptoms of NCLs are linked to a build-up of substances called lipopigments in the body’s tissues. These lipopigments are made up of fats and proteins. 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 accumulate and form deposits, which cannot be metabolized.

The biochemical defects causing NCLs are only now being identified. Scientists indicate that these abnormal deposits result from a shortage of enzymes normally responsible for the breakdown of lipopigments. Diseased cells produce inadequate amounts of enzymes or manufacture defective enzymes that function poorly. As a result, the cells cannot process and eliminate the lipopigments that occur within them, and the lipopigments accumulate. Scientists have not pinpointed what specific enzymes are at fault or determined how the stored lipopigments damage nerve cells.

How are these disorders diagnosed?

NCL is most often diagnosed by a neurologist, a doctor who specializes in disease of the brain and nervous system. In order to diagnose NCL, the neurologist may use some of the following diagnostic tests ( generally moving from least invasive test to most invasive):

Blood or urine tests. These tests may detect abnormalities such as elevated levels of chemicals.

Skin or tissue sampling. Examination of small pieces of tissue under an electron microscope may help identify typical NCL deposits.

Electroencephalogram or EEG. Recording electrical currents inside the brain may show tell-tale patterns in the brain’s electrical activity that suggests a patient has seizures.

Electrical studies of the eyes. These tests may detect various eye problems common in childhood NCLs.

Brain scans. Computed tomography (CT) uses x-rays and a computer to create a sophisticated picture of the brain’s tissues and structures. It may reveal brain areas that are decaying in NCL patients. Magnetic resonance imaging (MRI) uses a combination of magnetic fields and radio waves, instead of radiation, to create a picture of the brain.

Are there any treatments or cures?

Research into the genetic nature of the disorder, and possible treatments and cures, has been gaining momentum in the past few years. In the late 1990’s, researchers were able to identify the genes that were responsible for several of the forms of NCL. For example, in 1997, the gene for the late infantile NCL was named CLN2 and found to be located on chromosome 11.

Much of the research currently taking place is focused on introducing into the body the enzyme that is missing in those affected by NCL. The enzyme would then metabolize the excess lipopigment deposits. Since the excessive amounts of lipopigments seem to be the cause of the disorder, researchers understand that removing the deposits will stop the progress of the disorder and may lead to reversal of its symptoms.

Research is taking place in the following key areas:

Gene Transfer Therapy

The intent of this therapy is to introduce into the central nervous system the gene that is missing in those affected by NCL. The gene would then produce enzymes to metabolize the stored lipopigment deposits.

A major initiative took place at Cornell University’s Institute of Genetic Medicine. Since October 2000, the project moved rapidly through several stages of preliminary research and successful testing on both rodents and non-human primates. Clinical trials were done on both mildly and moderately progressed children of Late Infantile NCL, with the intent of proving the efficacy/safety of this enzyme therapy treatment (introducing enzyme directly into the brain via sterotactic surgery).

This project is progressed at such a rapid rate due to the support of Nathan’s Battle Foundation. When Nathan Milto was diagnosed with late infantile NCL in May 1999, his parents began raising funds for scientific research. They later entered into a formal agreement with the Institute of Genetic Medicine to perform a feasibility study to explore the viability of gene therapy as a cure for the disorder and then establish a detailed project to develop this cure. Additional information may be found at their website,

The Cornell group under Dr. Ron Crystal is currently working on a phase II of their treatment/therapy. This uses a different vector to carry the enzyme to the brain, and builds on the results they found in phase 1.

Enzyme Replacement Therapy

Enzyme replacement therapy is similar to gene replacement therapy in that it involves the introduction into the body of the missing enzyme rather than the gene that produces it. Currently Beverly Davidson’s team at Iowa University is working on using purkinje cells to deliver the missing enzyme, and target the brain, where they help populate the cells which have no functional copies of the enzyme transferred.
In previous research, a team of scientists conducted clinical trials using the enzyme phospholipase A1. Affected test subjects received injections of a manufactured enzyme which clears away the stored lipopigment. Enzyme replacement therapy has been used successfully to treat another storage disorder know as Gaucher’s Disease.

Stem cell research / therapy

Many NCL families in recent years have taken their children to China for stem cell brain surgery. (Colton is believed to be the first NCL child treated in India). This treatment is currently not available as a health treatment option for NCL in North America. StemCells Inc., a US company in Oregon did run a clinical trial 2006-09, where their proprietary neural cells were stereotactically implanted into the brains of late infantile (mildly progressed) NCL subjects. (they may have also used Infantile) The goal of this was to determine safety levels, and to move their cell line closer to being a source for medical use worldwide. (see They continue to be quite pleased with their results, and the results of the children who participated in their study.

Drug Replacement Therapy

Flupirtine is a drug which actively stops the neuron cells from dying through apoptosis. Several research projects have been conducted to define its effectiveness with those with NCL.

Additional information on research into NCL may be found on the website of Batten Disease Support and Research Association (BDSRA) at

Links — Where can I find more information?

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

Batten Disease Support and Research Association
120 Humphries Dr., Suite 2
Reynoldsburg, OH 43068
800-448-4570 or 740-927-4298

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

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

Office of Scientific and Health Reports Neurological Institute
P.O. Box 5801
Bethesda, Maryland 20824
(301) 496-5751
(800) 352-9424

Children’s Health System and University of Washington

Publishes GeneReviews, an online publication, funded by the National Institutes of Health (NIH). GeneReviews is expert-authored and peer-reviewed; it is intended to provide health care professionals with information about the use of genetic testing in patient diagnosis, management and genetic counselling.

Children Living with Inherited Metabolic Diseases

A national umbrella organization of the United Kingdom working on behalf of children, young people and families affected by metabolic diseases.

The New Zealand Lysosomal Storage Disease Support Group

Facilitates contacts, information sharing and support among affected people and their families, within New Zealand and internationally; advocates accelerated research into the causes and treatment of Lysosomal Storage Diseases and improvements to the treatment and care of affected people.

The Batten Support and Research Trust

Raises public awareness of Batten Disease/NCL by whatever means. Through awareness comes knowledge and through knowledge comes hope. Research is based on demand and demand is created by awareness.

The National Institute of Health

American governmental organization supporting medical and behavioural research. Its mission is science in pursuit of fundamental knowledge about the nature and behaviour of living systems and the application of that knowledge to extend healthy life and reduce the burdens of illness and disability.