What is batten disease?
Batten’s disease is the common name for a wide class of rare, fatal inherited disorders of the nervous system,
also known as neuronal ceroid lipofuscinosis, or NCL. In these diseases, a defect in a specific gene triggers a cascade of problems that interferes with a cell’s ability to recycle certain molecules.
The disease has several forms that share some of the same characteristics and symptoms, but vary in severity and age when symptoms begin to appear.
Each form is caused by a mutation in a different gene. Although “Batten’s disease” originally referred specifically to the juvenile-onset form of NCL,
the term Batten’s disease is increasingly used to describe all forms of NCL.
Most forms of Batten / NCL disease generally begin in childhood.
Children with the disease often appear healthy and develop normally before symptoms begin.
Children with infantile or late forms generally show symptoms before the age of 1 year.
Common symptoms for most forms include loss of vision, seizures, delay and eventual loss of previously acquired skills, dementia, and abnormal movements.
As the disease progresses, children may develop one or more symptoms including personality and behavior changes, clumsiness, learning difficulties, poor concentration, confusion, anxiety, difficulty sleeping, involuntary movements, and slow movements.
Over time, affected children may experience worsening attacks and progressive loss of language, speech, intellectual abilities (dementia), and motor skills.
Eventually, children with Batten’s disease become blind, wheelchair bound, bedridden, unable to communicate, and lose all cognitive functions.
There is no cure for these disorders, but the US Food and Drug Administration has approved a treatment for one of the forms (CLN2 disease) (see Treatment section).
Children with all forms of Batten disease have a much shorter life expectancy.
In general, the highest risk of premature death depends on the form of the disease and the age of the child at the onset of the disease.
Children with infantile Batten disease die prematurely,
often in early childhood, while those with late-onset forms can live from adolescence to age thirty.
If the disease develops in adulthood, symptoms tend to be milder and may not affect life expectancy.
Over time, Batten’s disease damages the brain and nervous system. There are four main types of this condition. These are its common symptoms:
- Changes in personality and behavior.
- Speech and motor problems that get worse over time
There are four main types of Batten disease. The type will determine the age at which symptoms occur and how quickly they develop.
causes of Batten disease?
Batten’s disease is an inherited genetic disorder that appears to affect the function of small bodies within cells called lysosomes.
Lysosomes are the cell’s “recycle bin” and regularly break down waste, protein, and natural fatty compounds called lipids into smaller components that can be discarded from the cell or recycled.
Lipids include fatty acids, oils, waxes, and sterols.
In Batten / NCL disease, mutated genes do not produce adequate amounts of proteins important for lysosomal function.
Each gene (representing a form of the disease) provides information for a specific protein that in turn is defective and does not occur.
These proteins are necessary for brain cells (neurons) and other cells to function efficiently.
Lack of a functional protein causes abnormal accumulation of “junk” material in lysosomes,
as well as abnormal accumulation of the residue called lipofuscin that occurs naturally as part of the lysosomal breakdown of lipids.
It is not known whether lipofuscin itself is toxic or whether the accumulation is a marker of altered lysosomal function.
Originally, doctors only referred to one form of NCL as Batten’s disease, but now the name refers to the group of disorders.
Of the four main types, all three that affect children cause blindness.
Congenital NCL affects babies and can cause them to be born with seizures and abnormally small heads (microcephaly).
It is very rare, and often results in death soon after a baby is born.
Infant NCL (INCL) generally appears between the ages of 6 months and 2 years.
It can also cause microcephaly, as well as sharp contractions (jerks) in the muscles.
Most children with INCL die before their 5th birthday.
Late childhood NCL (LINCL) generally begins between the ages of 2 and 4 with symptoms such as seizures that do not improve with medication.
Includes loss of muscle coordination. LINCL is usually fatal when the child is between 8 and 12 years old.
Adult NCL (ANCL) begins before age 40.
People who have it have shorter lives, but the age of death can vary from person to person.
ANCL symptoms are milder and tend to progress more slowly. This form of the disease does not cause blindness.
Are these disorders diagnosed?
After a review of the person’s individual and family medical history and a neurological examination,
various tests can be used to diagnose Batten’s disease and other neuronal ceroid lipofuscinosis. Currently,
most diagnoses of Batten disease are made through genetic testing. Possible diagnostic tests include:
DNA analysis / genetic testing can confirm the presence of a mutated gene that causes NCL disease, as well as be used in the prenatal (before birth) diagnosis of the disease.
Increasingly, NCL genes are included in commercially available epilepsy genetic panels that test multiple genes at the same time.
Measurement of enzyme activity can be used to confirm or rule out CLN1 and CLN2 disease.
Blood or urine tests can detect abnormalities that may indicate Batten’s disease.
For example, elevated levels of a chemical called dolichol are found in the urine of many people with NCL,
And the presence of abnormal white blood cells that contain holes or cavities,
called vacuolated lymphocytes, is common to certain mutations in the disease.
Skin or tissue sampling may show distinctive shapes formed by the accumulation of lipofuscin, some looking like crescents,
while others looking like fingerprints, when viewed under a special microscope.
Lipofuscins also turn greenish-yellow when viewed under an ultraviolet light microscope.
Electroencephalograms (EEG) monitor brain activity through the skull, using electrodes that are placed on the scalp.
Revealing patterns in the electrical activity of the brain suggest that an individual is having seizures and some patterns
Along with the findings on examination and medical history may strongly suggest a specific type of NCL disease.
Electrical studies of the eyes, which include visually evoked responses
(which measure electrical activity in the brain generated by sight) and electroretinograms (used to detect abnormalities with the retina),
can identify several common eye problems in various NCLs.
The greenish-yellow color of lipofuscins can sometimes be detected by examining the back of the eye.
They are now performed less frequently, since most diagnoses can be made with DNA tests.
Diagnostic images using computed tomography
(CT) and magnetic resonance imaging (MRI) can help doctors look for changes in the appearance of the brain….
Is there any treatment?
There is no known specific treatment that can reverse the symptoms of any form of Batten disease.
In 2017, the Food and Drug Administration approved an enzyme replacement therapy for CLN2 disease
(TTP1 deficiency) called cerliponase alfa (Brineura) that has been shown to slow or stop the progression of symptoms.
There are no treatments that can slow or stop disease progression for other NCL disorders.
Seizures can sometimes be reduced or controlled with anticonvulsant medications.
Other medications are available to treat anxiety, depression, parkinsonism (stiffness and difficulty walking / doing tasks), and spasticity (muscle stiffness). Additional medical problems can be adequately treated as they arise.
Physical and occupational therapy can help people with the disease maintain function for as long as possible.
Support groups can help affected children, adults and families share common concerns and experiences and cope with severe symptoms of the disease.
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