Clinical Trials within U.S.: Batten Disease

Batten Disease

Batten disease is named after the British pediatrician Frederick Batten, who first described the condition in 1903. This disease is the most common form of a group of disorders called neuronal ceroid lipofuscinosis, which are lysosomal storage disorders brought on by inherited genetic mutations in genes that provide cells with normally secreted housekeeping lysosomal enzymes. Lack of these enzymes causes a buildup of lipofuscin (aggregates of lipids and proteins) that leads to neuronal cell loss, primarily in the brain. Some physicians use the term Batten disease to describe all forms of neuronal ceroid lipofuscinosis, initially classified by age of onset (infantile, late infantile, and juvenile) and now more precisely classified in terms of the specific enzyme deficiencies causing the disease.

The disease is inherited in an autosomal recessive manner. Six genes have now been identified that cause different types of Batten disease in children or adults; more have yet to be identified. Two genes are related to two subtypes of neuronal ceroid lipofuscinosis: infantile and late infantile. These genes are CLN1, which codes for the enzyme palmityl—protein thioesterase 1 (PPT1), and CLN2, which codes for the enzyme tripepti—dyl peptidase I (TPP—I). The consequence of these gene mutations is either a defective or missing enzyme that leads to accumulation of lipofuscin—like fluorescent inclusions in various cell types. The diagnosis of Batten disease is based on the presence of these deposits in skin samples as well as other criteria.

Early symptoms of this disorder usually appear at age 4–10 years, with gradual onset of vision problems, including eye discoloration causing a milky fog gloss over the eyes, or seizures. Because vision loss is often an early sign of the condition, Batten disease may be first suspected during an eye exam. Often, an eye specialist or other physician may refer the child to a neurologist. Diagnostic tests for Batten disease include blood or urine tests, skin or tissue sampling, an electroencephalogram, electrical studies of the eyes, and brain scans.

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 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, and demented. Batten disease is often fatal by age 8–15 years.

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