Batten disease

A fatal disease of the nervous system that typically begins in childhood.

It is a terminal disease; life expectancy varies depending on the type or variation.

Its incidence is as high as one in 12,500 live births.

Its onset of symptoms is usually between 5 and 10 years of age.

It is often an autosomal recessive.

It is a disorder of neuronal ceroid lipofuscinoses (NCLs).

Associated with a life expectancy between eight and twelve years of age.

Frequency 3 per 100,000 births.

At least 20 genes have been identified in association with Batten disease.

Juvenile NCL, the most prevalent form of Batten disease, has been linked to mutations in the CLN3 gene.

Signs and symptoms of the disorder usually appear around ages 2–10, with gradual onset of vision problems or seizures.

There may be subtle personality and behavioral changes, slow learning or regression, repetitive speech or echolalia, clumsiness or stumbling.

Other findings include: slowing head growth in infants form, poor circulation in lower extremities, decreased body fat and muscle mass, curvature of the spine, hyperventilation and/or breath-holding spells, teeth grinding and constipation.

Affected children have mental impairment, worsening seizures and progressive loss of sight, speech and motor skills.

Females show first symptoms a year later than males, and on average die a year sooner.

Inherited in an autosomal recessive manner.

Neuronal ceroid lipofuscinoses (NCLs) are responsible for most pediatric neurodegenerative diseases.

Mutations in ten genes lead to the development of Batten disease.

The CLN3 gene is located on the short arm of chromosome 16 at gene position 12.1 (16p12.1), and mutations within this gene are the major cause of juvenile NCL.

73% of Batten disease cases are due to a 1.02-kb deletion within this gene, CLN3, which causes a truncated mutant gene product of only 181 amino acids in length when compared to the wild-type gene product of 438 amino acids in length.

The 181 amino acid mutant gene product is found to primarily localize to the endoplasmic reticulum and Golgi apparatus.

The precise function of the CLN3 gene product remains unknown.

Vision impairment is the most common symptom of the disease.

Occurrences in children are more prevalent than occurrences in adolescents or adults.

A fundus eye examination that aids in detection of common vision impairment abnormalities: granularity of the retinal pigment epithelium in the central macula .

To confirm the diagnosis: elevated levels of dolichol in urine have been found in many individuals with NCL, vacuolated lymphocytes, when combined with other findings that indicate NCL, is suggestive for the juvenile form caused by CLN3 mutations.

NCL deposits are common in tissues such as skin, muscle, conjunctiva, and rectum.

Electroencephalogram (EEG) assists in observing if the patient has seizures.

Visual-evoked responses and electroretinograms can detect various eye conditions common in childhood NCLs.

MRI imaging and CT brain scans can help reveal brain areas that are decaying, or atrophic, in persons with NCL.

Elevated levels of palmitoyl-protein thioesterase is involved in CLN1.

Acid protease is involved in CLN2, while Cathepsin D is involved in CLN10.

DNA analysis can confirm the diagnosis.

DNA analysis can also be used to detect unaffected carriers of this condition for genetic counseling, as it is possible to sequence all of the known NCL genes,

FDA has approved cerliponase alfa, to slow loss of walking ability (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency.

Brineura is the tradename.

Treatment is symptomatic and supportive.

Milasen, an antisense oligonucleotide drug for Batten disease.

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