Batten disease (also known as Spielmeyer-Vogt-Sjögren-Batten disease) is an extremely rare and fatal autosomal recessive neurodegenerative disorder that begins in childhood. It is the most common form of a group of disorders called the neuronal ceroid lipofuscinoses (NCLs). Although Batten disease is usually regarded as the juvenile form of NCL (or type 3), some physicians use the term Batten disease to describe all forms of NCL. Historically, the NCLs were classified by age of disease onset as infantile NCL (INCL), late infantile NCL (LINCL), juvenile NCL (JNCL) or adult NCL (ANCL). At least twenty genes have been identified in association with Batten disease, but juvenile NCL, the most prevalent form of Batten disease, has been linked to mutations in the CLN3 gene. Early signs and symptoms of the disorder usually appear around ages 2–10, with gradual onset of vision problems, or seizures. Early signs may be subtle personality and behavior changes, slow learning or regression, repetitive speech or echolalia, clumsiness, or stumbling. There may be slowing head growth in the infantile form, poor circulation in lower extremities (legs and feet), decreased body fat and muscle mass, curvature of the spine, hyperventilation and/or breath-holding spells, teeth grinding, and constipation. Over time, affected children suffer mental impairment, worsening seizures, and progressive loss of sight, speech and motor skills. Eventually, children with Batten disease become blind, bedridden, demented, and die. Batten disease is a terminal disease; life expectancy varies depending on the type or variation. Females with juvenile Batten disease show first symptoms a year later than males but on average die a year sooner.

Cause Batten disease is caused by genetic mutations that cause lipofuscins to accumulate within the body's tissues. These substances consist of fats and proteins and form certain distinctive deposits that cause the symptoms and can be seen under an electron microscope. The diagnosis of Batten disease is based on the presence of these deposits in skin samples as well as other criteria. Eight genes have now been identified that cause different types of Batten disease in children or adults, more having yet to be identified. Two of these genes encode enzymes. The function of most of these genes is still unknown. The identification of these genes opens up the possibility of gene replacement therapy or other gene-related treatments. Batten disease is very rare and occurs in an estimated 2 to 4 out of every 100,000 births in the United States. Genetics Batten disease is inherited primarily in an autosomal recessive pattern, but it varies by age. In cases involving children, it is only inherited as an autosomal recessive trait. In adults, the inheritance pattern is still autosomally recessive but there is also a chance of it being inherited in an autosomal dominant fashion as well. Eight genes have been identified in the variety of NCLs, mutations in which contribute to the development of the phenotypic trait of the disorders: CLN1 or PPT1, encodes an enzyme called palmitoyl-protein thioesterase 1 that is insufficiently active in Infantile NCL. CLN2 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. 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. Diagnosis In many instances, Batten disease is initially seen by an optometrist or ophthalmologist during an eye exam because one of the first signs is vision loss. Even though it is also seen in a variety of other diseases as well, a loss of ocular cells should be a warning sign of Batten Disease potentially being present. If Batten Disease is a possible diagnosis for an individual, a variety of tests are run to confirm including: 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 (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. 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 advanced have made it possible to sequence all of the known NCL genes, increasing the chances of finding the responsible mutation(s). History Batten disease is named after the British pediatrician Frederick Batten, who first described it in 1903. Also known as Spielmeyer-Vogt-Sjögren-Batten disease, it is the most common form of a group of disorders called neuronal ceroid lipofuscinosis (or NCLs). Although Batten disease is usually regarded as the juvenile form of NCL, some physicians use the term Batten disease to describe all forms of NCL.

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