What Is Batten Disease?

Batten disease is a rare group of genetic disorders that affect the body’s ability to get rid of cellular waste (lipids and proteins). As cellular waste builds up in the body (primarily in the brain, central nervous system, and retina), it can cause seizures, vision loss, cognitive problems, movement problems, and is eventually fatal. Fatality tends to occur in the late teens or early twenties. There is no cure for Batten disease.

There are 13 known types of Batten disease, each categorized within a group of disorders known as neuronal ceroid lipofuscinosis (NCL). Batten disease is a metabolic disorder that develops from a genetic mutation and significantly impacts the nervous system. Symptoms typically develop in childhood and can appear in babies, preteens, or teens. Since there is no cure for this disease, the main goal of treatment is to manage symptoms and improve a person’s quality of life.

Batten disease impacts about 3 out of 100,000 births in the United States. Both parents must carry the gene to pass it down and because it is a genetic disorder, siblings of children with Batten disease have a 25% chance of developing the disease. People of Scandinavian or Northern European descent have an increased likelihood of developing the disease. In Northern Europe, about 1 out of 25,000 births are born with Batten disease.

There are several types of Batten disease. Researchers have currently discovered 13 types. The 5 major types include:

• Congenital NCL. This is a rare type of Batten disease. Babies born with congenital NCL are born with abnormally small heads (microcephaly) and seizures. It is usually fatal soon after the baby is born.
• Infantile NCL (INCL, CLN1). This type typically develops between the age of 6 months and 2 years. It can cause microcephaly and severe muscle contractions. Most children with INCL die in early to mid-childhood. There is also a juvenile onset of CLN1, which develops around 5 or 6 years old. Children with juvenile onset may live into their teenage or young adult years because the disease progresses more slowly the later in age it develops.
• Late Infantile NCL (LINCL, CLN2). This type typically develops between the age of 2 and 4. It can cause seizures and losing the ability to walk and speak. It is usually fatal between the ages of 8-12. Although there is no cure for Batten disease, the Food and Drug Administration approved an enzyme replacement therapy for CLN2 called cerliponase alfa (Brineura). This medication helps to slow the progression of losing the ability to crawl or walk in patients 3 years of age or older with CLN2. The medication is administered as an infusion through an intraventricular access device.
• CLN3 disease. This type has a juvenile onset (ages 4-7). The first noticeable symptom is usually vision loss. Children with CLN3 may also start having seizures, cognitive issues, and behavioral problems around age 10. Seizures can be managed by anticonvulsant medication. There are also medications that can treat some of the symptoms that are similar to Parkinson’s disease (muscle rigidity or stiffness, muscle spasms, difficulty with moving and walking). Most people with CLN3 die between the age of 15 and 30.
• Adult NCL (ANCL, CLN4 or Kufs disease type B). This type develops before age 40 and consists of movement issues and early onset dementia. People with CLN4 may have a shorter lifespan, but others with the disease may have a normal lifespan. CLN4 symptoms develop and progress at a much slower rate and are milder in nature. This type of Batten disease does not lead to blindness.

Signs and Symptoms

The symptoms of Batten disease can vary in progression and presentation depending on the type of NCL or gene mutation. Specifically, the age that symptoms present may vary the progression and appearance of symptoms between individuals. Babies with Batten disease may develop normally for a time, hitting normal growth and development milestones, and then will stop progressing and will begin to regress and decline. The skills they had developed will deteriorate and this decline generally happens rapidly. Adults who develop Batten disease do not experience vision loss and usually have normal lifespans.

Symptoms include:

• Vision loss (this does not affect adults with Batten disease)
• Epilepsy/seizures
• Cognitive issues
• Speech problems (delays and stuttering)
• Coordination issues (clumsiness, balance, and movement problems)

Other issues that may develop later or at some point with the first set of symptoms include:

• Tics or tremors, muscle spasms, and muscle twitches (myoclonus)
• Changes in personality, mood, or behavior
• Hallucinations or episodes of psychosis
• Sleep disturbance
• Dementia
• Muscle spasticity (muscles that are consistently rigid, tight, or flexed)
• Muscle weakness in limbs which progresses to paralysis
• Heart problems (arrhythmia in teenagers and young adults)

Causes

Batten disease a hereditary and is caused when both parents pass down a copy of the genetic mutation. The gene mutation does not allow the body to break down cellular waste appropriately. The cellular waste consists of lipids, proteins, and sugars that the body is unable to break down. This waste builds up in cells throughout the body, specifically in the brain, central nervous system, and retina. The cellular waste buildup inhibits the body from functioning appropriately.

Risk Factors

The risk factor for developing Batten disease consists of both parents carrying the mutated gene. If both parents carry a copy of the mutated gene, there is a greater risk of a child being born with Batten disease. Additionally, a sibling of a child with Batten disease has a 25% chance of developing the disease.

Diagnosis

Batten disease is often hard to diagnose because symptoms overlap with many other diseases and disorders. Your child may first see an eye doctor or primary care physician before being referred to a neurologist. Your child’s doctor will perform an exam and take a thorough medical history. Additionally, there are several tests that can be administered to diagnose Batten disease.

Tests include:

• DNA test. A saliva or blood sample will be taken and sent to a lab for testing. Batten disease can only be diagnosed through a DNA test.
• Tissue sample (biopsy). This test will collect a tissue sample, usually from the skin, and will assess for atypically large deposits of lipofuscins. Lipofuscins are collections of fats and proteins that build up on the skin and other tissue.
• Eye exam. Your doctor will perform an electroretinography (ERG), which is used to assess the health of the retina and optic nerve. An ERG measures how the retina reacts to light.
• Blood or urinalysis. These tests detect certain abnormalities in the blood or urine that may indicate Batten disease.
• Electroencephalogram (EEG). This test uses patches placed on the scalp to detect electrical currents through the brain. The test allows doctors to see any signs or patterns of electrical activity in the brain that might indicate seizures.
• Imaging tests (MRI or CT scan). Imaging tests can identify abnormalities or changes in the brain that may indicate Batten disease.
• Enzyme level measurement. Some types of Batten disease involve a lack of specific enzymes, so enzyme testing can confirm or rule out certain types of Batten disease. 

Treatment

There is no known cure for Batten disease and all but 1 type ends in early death. Although there is no known cure, the Food and Drug Administration (FDA) has approved an enzyme replacement therapy for CLN2 disease called cerliponase alfa (Brineura). This medication helps to slow the progression of losing the ability to crawl or walk in patients 3 years of age or older with CLN2. It does not slow down any of the other symptom progression. The medication is administered as an infusion through an intraventricular access device. Other treatments for Batten disease include anticonvulsants to manage seizures and medications to treat muscle rigidity and spasms and difficulties with movement. Additionally, some people with Batten disease may benefit from physical therapy or occupational therapy.

Prevention

It is not possible to prevent Batten disease. If both parents carry a copy of the mutated gene, it is possible your child and their siblings will be born with the disease. Genetic counseling can provide insight into whether you or your spouse carry the gene, which is helpful data to know as you plan for a family. If you have anyone in your family or extended family who has or has had Batten disease, genetic counseling is strongly recommended.

Complications

There are several complications that come from developing Batten disease. Since there is no cure for Batten disease and is a progressive disorder, most symptoms get worse over time. Complications include:

• Vision loss and eventual blindness
• Cognitive decline
• Movement issues (muscle spasms and rigidity, constant muscle contraction, complete loss of the ability to walk or crawl)
• Behavioral and mood issues
• Early death