Rare Neurology News

Disease Profile

Neuronal ceroid lipofuscinosis 2

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Childhood

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ICD-10

E75.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

CLN2; Jansky-Bielschowsky disease; CLN2 disease, late infantile (subtype);

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases;

Summary

Neuronal ceroid lipofuscinosis 2 (CLN2) is a type of neuronal ceroid lipofuscinosis (NCL), a group of severe diseases that affect the nervous system. Symptoms of the CLN2 generally develop between ages two and four years, although later onset cases have been reported. Children with CLN2 may experience speech delay, seizures that do not respond to medications, loss of muscle coordination (ataxia), muscle twitches (myoclonus), loss of vision, developmental delay, and intellectual disability. Symptoms of CLN2 worsen as the child gets older (progressive).[1][2][3]

CLN2 is caused by changes (pathogenic variations) in the TPP1 gene and is inherited in an autosomal recessive manner.[4][3] Although there is no medication that can currently cure CLN2, in the Spring of 2017 both the United States Food and Drug Administration (FDA) and the European Commission approved the use of cerliponase alfa (brand name: Brineura) for children with CLN2. In clinical studies, cerliponase alfa was shown to slow down the progression of the disease.[5] In addition, other medications and therapies can help relieve some of the symptoms of CLN2.[1][2][3]

Please note: Batten disease originally referred specifically to the juvenile and most common form of NCL, now known as CLN3. However, the term Batten disease is increasingly used to describe all forms of NCL. All types of NCL also belong to a larger group of diseases known as lysosomal storage disorders.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormal nervous system electrophysiology
0001311
Ataxia
0001251
Autosomal recessive inheritance
0000007
Cerebral atrophy
Degeneration of cerebrum
0002059
Curvilinear intracellular accumulation of autofluorescent lipopigment storage material
0003205
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Increased extraneuronal autofluorescent lipopigment
0003463
Increased neuronal autofluorescent lipopigment
0002074
Myoclonus
0001336
Progressive visual loss
Progressive loss of vision
Progressive vision loss
Progressive visual impairment
Slowly progressive visual loss
Vision loss, progressive
Visual loss, progressive

[ more ]

0000529
Retinal degeneration
Retina degeneration
0000546
Seizure
0001250
Undetectable electroretinogram
0000550

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    • Cerliponase alfa(Brand name: Brineura) Manufactured by BioMarin Pharmaceutical, Inc.
      FDA-approved indication: To slow the progression of loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency.
      National Library of Medicine Drug Information Portal

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Neuronal ceroid lipofuscinosis 2. This website is maintained by the National Library of Medicine.
      • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Neuronal ceroid lipofuscinosis 2. Click on the link to view a sample search on this topic.

          References

          1. Mole SE, Williams RE. Neuronal Ceroid-Lipofuscinoses. GeneReviews. August 1, 2013; https://www.ncbi.nlm.nih.gov/books/NBK1428/.
          2. Chang CH. Neuronal Ceroid Lipofuscinoses. Medscape Reference. May 4, 2017; https://emedicine.medscape.com/article/1178391-overview.
          3. Williams RE, Adams HR, Blohm M, et al. Management Strategies for CLN2 Disease. Pediat Neurol. April 2017; 69:102-112. https://bdsra.org/wp-content/uploads/2014/06/Williams_2017_Management-strategies-for-CLN2-disease.pdf.
          4. CLN2 disease. Genetics Home Reference. November 2016; https://ghr.nlm.nih.gov/condition/cln2-disease.
          5. Markham A. Cerliponase Alfa: First Global Approval. Drugs. July 2017; 77(11):1247-1249. https://www.ncbi.nlm.nih.gov/pubmed/28589525.