Batten disease

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at September 20, 2016
StartDiseasesBatten disease

Batten disease is a rare neurodegenerative disorder that usually develops during childhood. Originally, Batten disease was only used as another term for juvenile neuronal ceroid lipofuscinose (NCL). However, it is now commonly used to describe all forms of NCL.

Contents

Definition & Facts

Batten disease, or NCL, is a progressive neurological disorder that is inherited through an autosomal recessive pattern. It includes five subtypes which are classified by the age in which they develop. They are congenital NCL, infantile NCL, late-infantile NCL, juvenile NCL, and adult NCL.

All cases of the disorder are rare, occurring in approximately 2 out of every 100,000 births in the United States. Batten disease is a type of lysosomal storage disorder. A lysosomal storage disorder is a type of ailment that disrupts a cell's ability to get rid of water. In Batten disease, this is due to a build-up of proteins and lipids.

Symptoms & Complaints

Symptoms attributed to Batten disease depend on the exact form of NCL that a patient has. Congenital NCL, the most severe form of Batten disease, develops at or soon after birth. These babies begin to suffer from respiratory failure, muscle rigidity, and seizures.

In addition, they have abnormally small heads, also known as microcephaly, and small brains. These infants suffer from a loss of brain cells in areas that control movement, thinking, and emotions. Their nerve cells also lack the myelin sheath. Infants suffering from this disorder often die hours to weeks after birth.

Infantile NCL, on the other hand, develops in babies from 6 months to two years old. This disorder progresses rapidly and, like other forms of NCL, is normally fatal. Most children with infantile NCL do not last past the age of five. Infants with this form of NCL have cognitive impairment and motor disabilities. They often develop seizures and vision problems, and they suffer from the loss of nerve cells and microcephaly.

Late-infantile NCL is similar to infantile NCL, except it usually does not develop until the ages of two to four. They suffer from all the same symptoms as infantile NCL, but they also suffer from developmental regression, and they usually do not live past their teen years.

Juvenile NCL occurs in children from the ages of five to ten, and those suffering from it rarely make it into their late twenties. Those with juvenile NCL suffer from developmental regression, like those with late-infantile NCL, as well as the other major symptoms, such as seizures and visual impairment. As the disease progresses, the symptoms become worse, and the child becomes unable to walk, blind, and suffers from dementia.

In contrast to the other forms of the disease, adult NCL is a milder version of the disorder that progresses more slowly and does not develop until around the age of 30. Those with the disorder suffer from many of the same symptoms as the other forms of NCL; however, visual impairment is not as likely. Like the other forms, it does shorten life expectancy; usually those with the disorder only live ten years after the disorder presents itself.

Causes

Batten disease is an autosomal recessive disorder, meaning a person must have two copies of the mutated gene for the disorder to arise. Each form of Batten disease comes from the mutation in different genes. Congenital NCL is caused by a mutation in the CTSD gene, which codes for the cathepsin D enzyme, which acts as a protease in lysosomes.

The mutation that causes infantile NCL arises in the PPT1 gene, which codes for the palmitoyl-protein thioesterase 1 enzyme. This enzyme removes long-chained fatty acids from proteins to help with the degradation of the protein. Most cases of late-infantile NCL are caused by a mutation in the TPP1 gene, which codes for the tripeptidyl peptidase 1 enzyme, and is used to breakdown peptides.

Juvenile NCL arises from a mutation in the CLN3 gene. The exact function of this gene is unknown. Mutations in the genes CLN1, CLN2, CLN5, CLN6, CLN8, and MFSD8 are also tied to the development of Batten disease.

In all cases, the mutations present cause issues in the lysosomes of the cells. This disruption in lysosome function leads to the build-up in fatty substances known as lipopigments. This accumulation causes the progressive death of cells, neurons being especially vulnerable to the lipopigment accumulation.

Diagnosis & Tests

The diagnosis of Batten disease requires the combination of numerous tests. Detection of autoflourescent ceroid lipofuscin deposits in the back of the eye is a common method used for the diagnosis of Batten disease. These deposits form pink and orange circular bands at the optic nerve and retina, which can be seen in the back of the eye.

Certain blood tests may be used in conjunction with this to help confirm a diagnosis. For instance, testing for abnormal white blood cells, such as those with vacuolated lymphocytes, is a common test used on patients suspected of having NCL. Urinalysis is also used to detect elevated levels of dolichol, which is often present in NCL patients.

In addition, skin samples and tissue samples are used to detect ceroid lipofuscin deposits, a hallmark sign of NCL. EEGs are used to detect seizures in patients, and they are used to analyze them to see if they are consistent with seizures associated with Batten disease.

Computed tomography (CT) scans and magnetic resonance imaging (MRI)s are frequently used in the diagnosis of Batten disease. These medical imaging techniques are used to show if a patient is developing shrinkage in certain areas of the brain. Enzyme activity is also a regular diagnostic test for NCL because in several forms of it, certain enzymes activity is greatly reduced or does not exist. Finally, genetic testing is used to evaluate if there are mutations in the genes known to cause Batten disease.

Treatment & Therapy

No specific form of treatment has yet been shown to halt or reverse the development of Batten disease. Instead, therapy and treatment is based merely on treating certain symptoms and focusing on quality of life. The seizures caused by NCL are often controlled or reduced through the use of anticonvulsants. However, in some cases, these medications are not effective.

Psychiatric and motor difficulties may also be treated with certain medications as they develop. Physical therapy is also used to help those suffering from the disorder retain function for as long as possible. Unfortunately, a patient with Batten will eventually reach a point where medications and therapy are no longer able to control the issue, and they will succumb to the disease. Studies are currently being performed to find better treatment options for those with this debilitating condition.

Prevention & Prophylaxis

There is no known method of prevention against Batten disease. Genetic counseling may be used to help with disease prevention. In these instances, parents must know that they are genetic carriers of the disease. Then, the possibilities of passing on the genetic mutation to a child can be assessed. This will allow prospective parent(s) to assess the risk of passing on the disorder to a child.

Preimplantation genetic diagnosis and prenatal testing may also help in prevention of the disease by allowing a parent to assess risk that a child will develop the disorder.