Batten Disease: Understanding Symptoms & Treatment Options

December 21, 2024

Batten disease is a rare disease affecting the nervous system. Weak eyesight, seizures, slowed growth rate, delays in cognitive learning, motor skills disability, and a lack of behavioral development are some of the typical manifestations of Batten disease.
The disease is caused by genetic mutations in the enzymes that remove wastes from the body. As a result of waste accumulation, nerve cells cannot function properly and eventually die.
The diagnosis of Batten disease often involves a combination of clinical evaluation, imaging studies, and genetic testing to confirm the presence of specific mutations. Unfortunately, there is currently no absolute cure for Batten disease. Its current treatment primarily focuses on symptom management and providing supportive care to improve the quality of life for those affected and their families.

What is Batten disease?

Batten disease, also known as neuronal ceroid lipofuscinosis (NCL), is a rare and terminal group of genetic disorders that cause a gradual and progressive loss of healthy nerve cells (neurons) in the brain, retina, and other tissues. It typically manifests in childhood but can also occur in infancy or adulthood, depending on the subtype. This condition leads to symptoms such as vision loss, seizures, slowed growth, motor difficulties, cognitive decline, and behavioral challenges.¹.

What Causes Batten Disease?

Batten disease is caused by genetic mutations in specific CLN genes (e.g., CLN1, CLN2, CLN3), which encode lysosomal enzymes. These enzymes are critical for removing waste and recycling cellular materials. Lysosomes act as the cell’s “recycling centers,” and their dysfunction leads to an accumulation of waste products like lipopigments in nerve cells. This accumulation disrupts cellular function and ultimately causes the death of neurons, classifying Batten disease as a lysosomal storage disorder.²
As a result, cells accumulate abnormal deposits of substances such as lipopigments, which interfere with normal cell function and ultimately lead to cell death in the nervous system.³

How Is Batten Disease Inherited?

The inheritance pattern of Batten disease is recessive. It means that a person will develop the disease only if they inherit two copies of the CLN mutation — one from each parent.⁴ Siblings of affected individuals face a 1 in 4 chance of developing the disease and a 50 percent likelihood of being carriers.⁵

Symptoms of Batten Disease

Individuals with Batten disease experience a range of neurological symptoms, including:

Vision loss
Seizures
Cognitive decline
Movement disorders
Behavioral changes
Progressive neurological deterioration
Loss of motor skills
Developmental regression
Sleep disturbances
Hyperactivity
Speech impairment
Loss of muscle coordination
Difficulty swallowing
Loss of independence in daily activities
Behavioral problems
Decline in academic or occupational performance

Children suffering from batten disease

These symptoms worsen over time as the disease progresses, ultimately leading to severe disability and premature death.

Types of Batten disease

Initially, only one form of NCL was known as Batten disease, but now the term encompasses a group of disorders. Among the four main types, the three affecting mainly the children lead to blindness.

Congenital NCL

Congenital NCL affects infants mainly at birth. The babies are born with small heads (microcephaly) and also present with seizures at birth.
It is a rare type and can result in the death of the baby shortly after birth.⁶

Infantile NCL

Infantile NCL typically begins between the ages of 6 months and two years. It progresses rapidly and can cause microcephaly and muscle contractions (jerks).
Most children with INCL give in to the disease in early to mid-childhood. Affected children may survive into their teenage or adult years if symptoms develop during adolescence.

Late infantile NCL

Late infantile NCL usually starts between the ages of 2 and 4 years. As compared to INCL, it has a slightly slower progression.
These children present with seizures and speech problems and show a gradual loss of walking abilities. These children usually die between the ages of 8 to 12.
In 2017, the FDA approved cerliponase alfa (Brineura) as an enzyme replacement therapy for CLN2 disease. It has been shown to mitigate the decline in mobility among symptomatic pediatric patients aged three and above.⁷ Brineura is introduced into the cerebrospinal fluid via a surgically implanted reservoir and catheter in the head.

Juvenile NCL

Juvenile NCL typically begins between the ages of 5 and 10. The typical symptoms are vision loss, seizures, and problems with learning and behavioral development. Visual loss occurs at 5 to 7 years of age, while learning problems with cognitive decline and seizures occur at 10.
Antiseizure medications may help control or reduce seizures. Teenagers develop Parkinsonism-like symptoms, which can be managed with medication. Most children with CLN3 disease die between the ages of 15 and 30.

Adult-Onset NCL

Adult-onset NCL (CLN4 or Kufs disease type B) usually begins in early adulthood and progresses more slowly than the other forms.
ANCL symptoms are milder and progress more slowly. This form of the disease does not lead to blindness.⁸
Patients experience movement difficulties and early dementia. While life expectancy is shorter, the age of death varies.

How Is Batten Disease Diagnosed?

Batten disease is frequently misdiagnosed due to its rarity and overlapping symptoms with other conditions. Vision loss often serves as an initial indicator. Doctors must carefully check infants and toddlers for neurological and eye problems to confirm the Batten disease.
Genetic testing and enzyme activity tests are now standard methods for diagnosis, especially in developed countries.⁹
Multiple examinations and tests may be necessary before a definitive diagnosis is reached.
Referral to neurologists for further evaluation is common in suspected cases.

Genetic Tests

Doctors use genetic testing to identify mutations in specific genes linked to Batten disease.
Newer methods like genomic sequencing help identify mutations more accurately, especially in cases with unusual symptoms.

Biochemical Tests

Enzyme activity tests can also confirm different forms of the disease. These tests are reliable and can be performed on various samples, such as blood, urine, or skin biopsy.

Neuropathology

Batten disease causes significant damage to the brain and nervous system. Changes in brain tissue, like neuron loss and buildup of certain substances, are typical.
Specific brain regions, like the cortex and cerebellum, are affected differently depending on the disease variant.
CT scans or MRIs assist in identifying brain changes associated with Batten disease. Electroencephalograms (EEGs) also help record brain electrical activity to detect potential seizures.

Visual Assessment

Vision problems, including retinal damage, are also common in Batten disease. Examination of tissue samples or eye observations can reveal the presence of characteristic deposits, sometimes visible as pink and orange circles known as “bull’s eye” formations.

Treatment Options Available for Batten Disease

The FDA recently authorized Cerliponase alfa (Brineura™) as a remedy for late-infantile-onset neuronal ceroid lipofuscinosis (CLN2) disease. Extensive clinical investigations revealed that Brineura™ halted the walking and speech difficulties among CLN2 patients.
Sadly, there are no other tailored treatments accessible to stall or reverse the symptoms of other NCL types. Brineura™ exclusively addresses CLN2-type Batten Disease. Nonetheless, supportive care strategies can aid in symptom management and enhance the quality of life for those affected. Some supportive measures include:

Seizure management with antiepileptic medications.
Physical therapy to maintain mobility and motor function.
Occupational therapy to support daily activities and independence.
Speech therapy to address communication difficulties.
Vision aids and support for individuals experiencing vision loss.
Palliative care provides comfort and support for both the individual and their family.
In cases where eating ability declines significantly, gastrostomy tube placement may be necessary to ensure adequate nutrition and weight maintenance.

Batten Disease Vs. Sanfilippo Syndrome

Although both the Batten disease and Sanfilippo syndrome are lysosomal storage diseases, they are different from each other in various aspects:

Genetic Mutation

Batten disease has different types caused by gene mutations like CLN1, CLN2, and CLN3.
On the other hand, Sanfilippo syndrome is mainly linked to mutations in genes like SGSH, NAGLU, HGSNAT, or GNS.

Enzyme Deficiency

In both diseases, different enzymes are deficient. For example, children with Sanfilippo syndrome cannot break down complex carbohydrates, while individuals with Batten disease cannot process lipoproteins and other cellular waste materials.
Both conditions cause the accumulation of these materials that impair normal cellular function.

Symptoms & Onset

Sanfilippo syndrome occurs at the age of 2 to 6 years. This disease can occur both in childhood and adulthood as well.

Prognosis & Life Expectancy For Batten Disease

Life expectancy and prognosis of Batten disease varies with its types.

Subtype Of Batten Disease	Life Expectancy
Infantile NCL	Mid-childhood
Late Infantile NCL	8-10 years of age
Juvenile NCL	Late teenage
Adult-onset NCL	Normal life span

Conclusively, Battens disease, also known as Neuronal Ceroid Lipofuscinosis (NCL), is a rare, inherited condition that impacts the nervous system. This process displays a range of symptoms, such as vision loss, seizures, cognitive decline, and movement disorders. Unfortunately, the treatment is not about the cure but symptom management and quality of life improvement. Genetic testing is essential to diagnosis.

Refrences

1
Dolisca, S. B., Mehta, M., Pearce, D. A., Mink, J. W., & Maria, B. L. (2013). Batten disease: clinical aspects, molecular mechanisms, translational science, and future directions. Journal of Child Neurology, 28(9), 1074–1100. https://doi.org/10.1177/0883073813493665
2
Johnson, T. B., Cain, J. T., White, K. A., Ramirez-Montealegre, D., Pearce, D. A., & Weimer, J. M. (2019). Therapeutic landscape for Batten disease: current treatments and future prospects. Nature reviews. Neurology, 15(3), 161–178. https://doi.org/10.1038/s41582-019-0138-8
3
Abou Sawan, S., Mazzulla, M., Moore, D. R., & Hodson, N. (2020). More than just a garbage can: emerging roles of the lysosome as an anabolic organelle in skeletal muscle. American journal of physiology. Cell physiology, 319(3), C561–C568. https://doi.org/10.1152/ajpcell.00241.2020
4
Johnson, T. B., Cain, J. T., White, K. A., Ramirez-Montealegre, D., Pearce, D. A., & Weimer, J. M. (2019). Therapeutic landscape for Batten disease: current treatments and future prospects. Nature reviews. Neurology, 15(3), 161–178. https://doi.org/10.1038/s41582-019-0138-8
5
Gulani A, Weiler T. Genetics, Autosomal Recessive. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546620/
6
Schulz, A., Kohlschütter, A., Mink, J., Simonati, A., & Williams, R. (2013). NCL diseases – clinical perspectives. Biochimica et biophysica acta, 1832(11), 1801–1806. https://doi.org/10.1016/j.bbadis.2013.04.008
7
Specchio, N., Pietrafusa, N., & Trivisano, M. (2020). Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy. Therapeutics and clinical risk management, 16, 213–222. https://doi.org/10.2147/TCRM.S241048
8
Berkovic, S. F., Staropoli, J. F., Carpenter, S., Oliver, K. L., Kmoch, S., Anderson, G. W., Damiano, J. A., Hildebrand, M. S., Sims, K. B., Cotman, S. L., Bahlo, M., Smith, K. R., Cadieux-Dion, M., Cossette, P., Jedličková, I., Přistoupilová, A., Mole, S. E., & ANCL Gene Discovery Consortium (2016). Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease). Neurology, 87(6), 579–584. https://doi.org/10.1212/WNL.0000000000002943
9
Johnson, T. B., Cain, J. T., White, K. A., Ramirez-Montealegre, D., Pearce, D. A., & Weimer, J. M. (2019). Therapeutic landscape for Batten disease: current treatments and future prospects. Nature reviews. Neurology, 15(3), 161–178. https://doi.org/10.1038/s41582-019-0138-8

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