What is Batten Disease?

Batten Disease is named after the British pediatrician, Frederick Batten, who first described it in 1903. 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 include Infantile and Late Infantile forms of NCL.

These forms of NCL are classified by age of onset and have the same basic cause, symptoms and outcome. Over time, affected children suffer mental impairment, 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 nor preventable.

What are the forms of NCL/Batten Disease?

There are four 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 noticeable at different ages and progress at different rates.

• Infantile NCL (Santavuori-Haltia disease): begins between 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.

NCL/Batten Disease is relatively rare, occurring in an estimated 2 to 4 of every 100,000 births in the United States. The disease has been identified worldwide.

What causes this disease?

Symptoms of Batten Disease are linked to a buildup of substances called lipopigments in the body’s tissues. Lipopigments are made up of fats and proteins. Their name comes from the technical word lipo, which means fat, and from the term pigment because lipopigments take on a greenish-yellow color when viewed under an ultraviolet light microscope.

The lipopigments build up in cells of the brain, eye, skin, muscle, and many other tissues. Inside the cells, these pigments form deposits with unique 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.

Childhood NCLs are autosomal recessive disorders; which means they occur only when a child inherits two copies, one from each parent, of the defective gene. 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 a copy of the defective gene, becoming a carrier.

Research

The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institute of health (NIH), is responsible for supporting and conducting research on the central nervous system and brain. The Batten Disease Support and Research Association and the Children’s Brain Diseases Foundation also provide financial assistance for research.

In September 1995, The International Batten Disease Consortium announced the identification of the gene for the juvenile form of Batten Disease. The specific gene, CLN3, located on Chromosome 16, has a deletion or piece missing.

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 Late Infantile form of Batten Disease/NCL. The gene, CLN2, is located on chromosome 11.

It was discovered that the Infantile and Late Infantile diseases are missing key lysosomal enzymes, known as Palmitoyl Protein Thioesterase 1 (PPT1) in Infantile NCL and Tripeptidyl Peptidase 1 (TPP1) in Late Infantile NCL.

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.

Treatment

Although there is no treatment that can stop or reverse the symptoms of Batten Disease, seizures can be controlled with anticonvulsant drugs. Physical, occupational and speech therapy may help patients retain as much of their abilities for as long as possible. AND there are experimental treatments showing great promise for the benefit of children with Batten’s Disease.

Gene Transfer Therapy

For Late Infantile NCL , there is a gene therapy clinical trial at Weill Medical College of Cornell University in New York sponsored by the National Institute of Health. This was originally funded by several families under Nathan’s Battle Foundation started in June 2004. It involves a procedure where an injection of the enzyme producing gene (CLN2) goes into the brain of a child with Batten Disease. During the first phase of this trial, the results showed significant slowing of the disease’s progression at the 18 month follow up. The sons of the Nathan’s Battle Foundation founder, Nathan and P.J., were in the first trial and have no further progression of their disease, however both remain severely handicapped. There will be a Phase 2 of this clinical trial opening in the next 3-6 months, as reported by one of the directors on May 20, 2009.

Stem Cell Therapy

At Doernbecher Children’s Hospital at Oregon Health & Science University, Dr. Nathan Selden and Dr. Robert Steiner began a clinical study where neural stem cells were injected into the brain of a six year old child suffering from Batten Disease. This child could no longer walk or talk. This child was one of six to receive the injection of a stem cells from Stem Cells Inc., a Palo Alto biotech company. In the month that followed, the child recovered enough to return home. It was reported that there were some signs of speech.

China also has clinics which offer stem cell therapy for children with Batten Disease. Some parents opt for this therapy and spend 5 to 6 weeks in China to receive stem cell injections through the spinal cord fluid. Although this approach is not generally supported by the US, parents do see improvement in their child’s condition. The clinics in China offer children the chance to slow the progression of the disease, not cure it.