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 behavioUr changes, slow learning, clumsiness, or stumbling. Over time, affected children suffer cognitive 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-Sjogren-Batten 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.
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 Santavuori-Haltia 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 Jansky-Bielschowsky 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 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.
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 colour 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.
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.