Neuronal Ceroid Lipofuscinosis

Written byVasudha Rao

Last updated November 4, 2022

What Is Neuronal Ceroid Lipofuscinosis?

Neuronal ceroid lipofuscinosis represents a group of rare childhood neurodegenerative diseases characterized by abnormal build up of lipofuscin, a waste product that is normally recycled and removed. In neuronal ceroid lipofuscinosis, lipofuscin builds up in the neuronal tissues including the brain, retina, and peripheral nerves. The most common type of neuronal ceroid lipofuscinosis that affects the eye is Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), also known as Batten disease. Neuronal ceroid lipofuscinosis (NCL) disorders cause rapid vision loss, with profound vision loss occurring within the span of a few months. NCL typically results from genetic mutations and causes blindness by the age of six years old.

Key Takeaways

Neuronal ceroid lipofuscinosis, also known as Batten Disease, are rare genetic neurodegenerative disorders that affect the eyes and central nervous system.
Neuronal ceroid lipofuscinosis is caused by the abnormal accumulation of lipofuscin, a cellular waste material that is toxic to brain cells.
Hallmarks of neuronal ceroid lipofuscinosis are blindness, seizures, dementia, and loss of cognitive functions in childhood.

Take our AI Powered Eye Quiz

GET 20% OFF

Understanding Neuronal Ceroid Lipofuscinosis

Neuronal ceroid lipofuscinoses (NCL) are neurodegenerative disorders caused by accumulation of lipofuscin. The accumulation of lipofuscin leads to rapid and progressive decline of vision, speech, movement, and cognitive ability. Children with NCL typically begin having seizures around the age of three. They become unable to walk, talk, or swallow, and often require a wheelchair. Some children with NCL may have premature death by the early twenties, depending on the type of NCL and the age of disease onset.

NCL has an autosomal recessive pattern of genetic inheritance. There are at least 13 distinct forms of NCL, denoted by CLN1 through CLN14. All of the different types of NCL have different symptoms and clinical profiles, so they are not interchangeable. For example, in infantile Type 1 (CLN1), seizure frequency tends to decrease in the later stages of the disease. CNL5 can cause macular degeneration. Juvenile neuronal ceroid lipofuscinosis (JNCL) is known as Batten disease and it is the most common type of NCL in the United States.

Pathology

NCL is caused by the toxic buildup of a substance called lipofuscin. Lipofuscin is an orange pigment that accumulates in lysosomes because they are unable to properly degrade it. In the retina, lipofuscin is the byproduct of incomplete degradation of photoreceptor outer segments. Lipofuscin in the retina indicates that the retinal pigment epithelium cells are sick and undergoing cell death.

Lipofuscin accumulation in the retina occurs with various conditions, including:

Juvenile neuronal ceroid lipofuscinosis (aka Batten disease)
Age-related macular degeneration
Stargardt disease
Best disease
Choroidal melanoma
Hydroxychloroquine (Plaquenil) medication toxicity

Diagnosis

Genetic testing is the gold standard diagnostic method that accurately identifies the exact type of NCL. An eye doctor can detect the loss of retinal pigment epithelial cells, and buildup of lipofuscin in the retina, using a few different tests:

Fundus Autofluorescence (FAF): This imaging technique characterizes the health of the retinal pigment epithelium (RPE) using fluorophores.
Dilated Eye Exam: After dilating the eyes, an eye doctor can check the health of the retina using special types of lenses. Common clinical signs of Batten disease in the retina include bull’s eye maculopathy, optic nerve atrophy, and vascular attenuation.
Optical Coherence Tomography (OCT): This imaging technique microscopically analyzes the layers of the retina to determine if the retinal pigment epithelium is abnormal.
Visual Field Test: This test measures the peripheral vision to determine if there is vision loss.
Electroretinography (ERG): This test measures electrical activity generated by the retina.

Treatment

Currently, only one FDA-approved drug is available to treat NCL. This drug is called Brineura (cerliponase alfa), and is only approved for a specific type of Batten disease called Jansky-Bielschowsky disease. Brineura is an enzyme replacement therapy that slows the build up of lipofuscin. Brineura may preserve motor functions such as walking, but not protect against blindness. Children with NCL can benefit from low-vision services to learn how to maximize their remaining vision.

Sources

Naseri, Nima, et al. “Autosomal Dominant Neuronal Ceroid Lipofuscinosis: Clinical Features and Molecular Basis.” Clinical Genetics, vol. 99, no. 1, 1 Jan. 2021, pp. 111–118, www.ncbi.nlm.nih.gov/pmc/articles/PMC7899141/, 10.1111/cge.13829.
‌“Batten Disease – EyeWiki.” Eyewiki.aao.org, eyewiki.aao.org/Batten_Disease. Accessed 3 Aug. 2022.
“Batten Disease Fact Sheet.” National Institute of Neurological Disorders and Stroke, U.S. Department of Health and Human Services, www.ninds.nih.gov/batten-disease-fact-sheet.
Kohlschütter, Alfried, et al. “Current and Emerging Treatment Strategies for Neuronal Ceroid Lipofuscinoses.” CNS Drugs, vol. 33, no. 4, 15 Mar. 2019, pp. 315–325, 10.1007/s40263-019-00620-8. Accessed 21 Sept. 2021.
Kaminiów, Konrad, et al. “Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis.” International Journal of Molecular Sciences, vol. 23, no. 10, 20 May 2022, p. 5729, 10.3390/ijms23105729. Accessed 20 July 2022.
Nelvagal, Hemanth R., et al. “Pathomechanisms in the Neuronal Ceroid Lipofuscinoses.” Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, vol. 1866, no. 9, 1 Sept. 2020, p. 165570, www.sciencedirect.com/science/article/pii/S0925443919302935?via%3Dihub, 10.1016/j.bbadis.2019.165570. Accessed 3 Aug. 2022.