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Genetics Home Reference: your guide to understanding genetic conditions
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Late-infantile neuronal ceroid lipofuscinosis

Reviewed August 2013

What is late-infantile neuronal ceroid lipofuscinosis?

Late-infantile neuronal ceroid lipofuscinosis (NCL) is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin in late infancy or early childhood. The initial features usually include recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision impairment. Late-infantile NCL affects motor skills, such as sitting and walking, and speech development. This condition also causes the loss of previously acquired skills (developmental regression), progressive intellectual disability, and behavioral problems. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens.

Late-infantile NCL is one of a group of NCLs (collectively called Batten disease) that affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different types of NCLs are distinguished by the age at which signs and symptoms first appear.

How common is late-infantile neuronal ceroid lipofuscinosis?

The prevalence of late-infantile NCL is unknown. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide. NCLs are more common in Finland, where approximately 1 in 12,500 individuals are affected.

What genes are related to late-infantile neuronal ceroid lipofuscinosis?

Mutations in the TPP1 gene cause most cases of late-infantile NCL. Mutations in the CLN5, CLN6, CLN8, MFSD8, and PPT1 genes each account for a small percentage of cases.

The TPP1 gene produces an enzyme called tripeptidyl peptidase 1. This enzyme is found in cell structures called lysosomes, which digest and recycle different types of molecules. Tripeptidyl peptidase 1 breaks down protein fragments, known as peptides, into their individual building blocks (amino acids).

The proteins produced from the other genes involved in this condition are active either in lysosomes or in another cell compartment called the endoplasmic reticulum. The endoplasmic reticulum is involved in protein production, processing, and transport. Within these cell structures, the proteins largely play roles in the breakdown of other proteins or substances.

Mutations in the TPP1, CLN5, CLN6, CLN8, MFSD8, or PPT1 gene usually reduce the production or activity of the particular protein or enzyme made from the gene. In many cases, a reduction in functional protein or enzyme results in incomplete breakdown of certain proteins and other materials. These materials accumulate in the lysosome forming fatty substances called lipopigments. In some cases, it is unclear what causes the buildup of lipopigments. In late-infantile NCL, these accumulations occur in cells throughout the body, but neurons seem particularly vulnerable to damage caused by lipopigments and a decrease in specific protein function. The progressive death of cells in the brain and other tissues leads to the signs and symptoms of late-infantile NCL.

Related Gene(s)

Changes in these genes are associated with late-infantile neuronal ceroid lipofuscinosis.

  • CLN5
  • CLN6
  • CLN8
  • MFSD8
  • PPT1
  • TPP1

How do people inherit late-infantile neuronal ceroid lipofuscinosis?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of late-infantile neuronal ceroid lipofuscinosis?

These resources address the diagnosis or management of late-infantile neuronal ceroid lipofuscinosis and may include treatment providers.

  • Gene Review: Neuronal Ceroid-Lipofuscinoses (http://www.ncbi.nlm.nih.gov/books/NBK1428)
  • Genetic Testing Registry: Ceroid lipofuscinosis, neuronal, 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1876161)
  • Genetic Testing Registry: Ceroid lipofuscinosis neuronal 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1850442)
  • Genetic Testing Registry: Ceroid lipofuscinosis neuronal 6 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1866282)
  • Genetic Testing Registry: Ceroid lipofuscinosis neuronal 7 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1838571)
  • Genetic Testing Registry: Ceroid lipofuscinosis neuronal 8 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1838570)
  • Genetic Testing Registry: Late-infantile neuronal ceroid lipofuscinosis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0022340)
  • NYU Langone Medical Center (http://www.med.nyu.edu/content?ChunkIID=23620)

You might also find information on the diagnosis or management of late-infantile neuronal ceroid lipofuscinosis in Educational resources (http://www.ghr.nlm.nih.gov/condition/late-infantile-neuronal-ceroid-lipofuscinosis/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/late-infantile-neuronal-ceroid-lipofuscinosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about late-infantile neuronal ceroid lipofuscinosis?

You may find the following resources about late-infantile neuronal ceroid lipofuscinosis helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for late-infantile neuronal ceroid lipofuscinosis?

  • Jansky-Bielschowsky disease
  • late-infantile Batten disease
  • LINCL
  • neuronal ceroid lipofuscinosis, late-infantile

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about late-infantile neuronal ceroid lipofuscinosis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding late-infantile neuronal ceroid lipofuscinosis?

acids ; ataxia ; autosomal ; autosomal recessive ; breakdown ; cell ; ceroid ; disability ; endoplasmic reticulum ; enzyme ; epilepsy ; gene ; inherited ; lysosome ; motor ; myoclonus ; nervous system ; prevalence ; protein ; recessive ; regression

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Getty AL, Pearce DA. Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function. Cell Mol Life Sci. 2011 Feb;68(3):453-74. doi: 10.1007/s00018-010-0468-6. Epub 2010 Aug 1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20680390?dopt=Abstract)
  • Jalanko A, Braulke T. Neuronal ceroid lipofuscinoses. Biochim Biophys Acta. 2009 Apr;1793(4):697-709. doi: 10.1016/j.bbamcr.2008.11.004. Epub 2008 Nov 24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19084560?dopt=Abstract)
  • Kousi M, Lehesjoki AE, Mole SE. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum Mutat. 2012 Jan;33(1):42-63. doi: 10.1002/humu.21624. Epub 2011 Nov 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21990111?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2013
Published: September 8, 2014