By: Imogen Ronde
What is Neuronal Ceroid Lipofuscinoses?
Neuronal Ceroid Lipofuscinoses are a group of rare disorders of the nerve cells. They include Kufs or Parry disease, Batten disease, and Jansky-Bielschowsky disease (Neuronal ceroid lipofuscinoses (NCL): Medlineplus medical encyclopedia). Neuronal Ceroid Lipofuscinoses are classified by the affected gene, which can be any one of eight: CLN1, CLN2, CLN3, CLN5, CLN6, CLNJ, CLN8 and CLN10. Each gene mutation can present at different life stages and have different associated symptoms. For example, a mutation in CLN3 can cause blindness, but it does not necessarily occur with other CLN gene mutations.
History:
The first described case of Neuronal Ceroid Lipofuscinoses was a report on four siblings in Norway that presented with progressive visual loss, cognitive decline, seizures, and premature death. Unfortunately, this report was unnoticed for 150 years. In the early 19th century, B. Sachs, a neurologist, coined the term “amaurotic familial idiocy” to describe this group of symptoms. Later, Kufs described adult-onset cases, and Batten and Spielmeyer distinguished different features, leading to the classification of these “storage diseases” (Simonati & Williams, 2022).
What causes Neuronal Ceroid Lipofuscinoses?
Neuronal Ceroid Lipofuscinoses are caused by mutations in any of several genes. These mutations are also inherited in “an autosomal recessive manner,” although one type of mutation is inherited in an autosomal dominant manner (Adult neuronal ceroid lipofuscinosis 2020). The affected genes all produce proteins, which, when the gene is mutated, become “deficient, absent, or ineffective” (Adult neuronal ceroid lipofuscinosis 2020). These proteins interfere with the breakdown of lipids, which then accumulate within the nerve cells and other body tissues (Adult neuronal ceroid lipofuscinosis 2020).
Signs and Symptoms:
Due to the many different types of Neuronal Ceroid Lipofuscinoses, there are a wide variety of symptoms that can be different from patient to patient. These include seizures, speech delays, ataxia, loss of motor skills, cognitive decline, visual impairment, myoclonus, dementia, personality changes, psychiatric symptoms like aggression, and extrapyramidal symptoms (Neuronal Ceroid Lipofuscinoses (NCL): Choc 2022).
How is it diagnosed?
There are multiple tests which are used to confirm a diagnosis of any of the Neuronal Ceroid Lipofuscinoses. These can include blood or urine tests to detect abnormalities, measuring enzyme activity for CLN1 or CLN2, DNA analysis, electroencephalograms to look for typical seizures, eye studies to check for conditions typical of CLN3, CT or MRI scans to study atrophic brain areas, and tissue sampling to look for deposits typical of Neuronal Ceroid Lipofuscinoses (Neuronal Ceroid Lipofuscinoses (NCL): Choc 2022).
Management and treatment:
The only form of Neuronal Ceroid Lipofuscinoses which has any treatment available is CLN2. Brineura has been shown to “slow or even stop the rate that walking, and speech were lost” (Neuronal Ceroid Lipofuscinoses (NCL): Choc 2022). There are no other treatments for other forms of Neuronal Ceroid Lipofuscinoses other than symptom control, for example seizures can be reduced with antiepileptic drugs, and physical therapy “may help patients retain motor functioning as long as possible” (Neuronal Ceroid Lipofuscinoses (NCL): Choc 2022).
Prognosis:
Outlook for Neuronal Ceroid Lipofuscinoses depends on the age of onset. Younger patients are at greater risk for disability, including blindness and mental problems, as well as early death. Patients who develop the disease in adulthood have milder symptoms, no vision loss, and normal life expectancy (Neuronal ceroid lipofuscinoses (NCL): Medlineplus medical encyclopedia).
Resources:
Adult neuronal ceroid lipofuscinosis. NORD (National Organization for Rare Disorders). (2020, March 26). Retrieved June 20, 2022, from https://rarediseases.org/rare-diseases/kufs-disease/
Jalanko, A., & Braulke, T. (2008, November 24). Neuronal ceroid lipofuscinoses. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research. Retrieved June 20, 2022, from https://www.sciencedirect.com/science/article/pii/S0167488908003996
Neuronal Ceroid Lipofuscinoses (NCL): Choc. Children’s Health Orange County. (2022, April 22). Retrieved June 20, 2022, from https://www.choc.org/programs-services/metabolic-disorders/neuronal-ceroid-lipofuscinoses-ncl/#:~:text=The%20neuronal%20ceroid%20lipofuscinoses%20(NCLs,referred%20to%20as%20Batten%20disease.
Simonati, A., & Williams, R. E. (1AD, January 1). Neuronal ceroid lipofuscinosis: The multifaceted approach to the clinical issues, an Overview. Frontiers. Retrieved June 20, 2022, from https://www.frontiersin.org/articles/10.3389/fneur.2022.811686/full
U.S. Department of Health and Human Services. (n.d.). Neuronal ceroid lipofuscinosis – about the disease. Genetic and Rare Diseases Information Center. Retrieved June 20, 2022, from https://rarediseases.info.nih.gov/diseases/10739/neuronal-ceroid-lipofuscinosis
U.S. National Library of Medicine. (n.d.). Neuronal ceroid lipofuscinoses (NCL): Medlineplus medical encyclopedia. MedlinePlus. Retrieved June 20, 2022, from https://medlineplus.gov/ency/article/001613.htm
