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Genetics Home Reference: your guide to understanding genetic conditions
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Congenital neuronal ceroid lipofuscinosis

Reviewed July 2013

What is congenital neuronal ceroid lipofuscinosis?

Congenital neuronal ceroid lipofuscinosis (NCL) is an inherited disorder that primarily affects the nervous system. Soon after birth, affected infants develop muscle rigidity, respiratory failure, and prolonged episodes of seizure activity that last several minutes (status epilepticus). It is likely that some affected individuals have seizure activity before birth. Infants with congenital NCL have unusually small heads (microcephaly) with brains that may be less than half the normal size. There is a loss of brain cells in areas that coordinate movement and control thinking and emotions (the cerebellum and the cerebral cortex). Affected individuals also lack a fatty substance called myelin, which protects nerve cells and promotes efficient transmission of nerve impulses. Infants with congenital NCL often die hours to weeks after birth.

Congenital NCL is the most severe form 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 congenital neuronal ceroid lipofuscinosis?

Congenital NCL is the rarest type of NCL; approximately 10 cases have been described.

What genes are related to congenital neuronal ceroid lipofuscinosis?

Mutations in the CTSD gene cause congenital NCL. The CTSD gene provides instructions for making an enzyme called cathepsin D. Cathepsin D is one of a family of cathepsin proteins that act as proteases, which modify proteins by cutting them apart. Cathepsin D is found in many types of cells and is active in lysosomes, which are compartments within cells that digest and recycle different types of molecules. By cutting proteins apart, cathepsin D can break proteins down, turn on (activate) proteins, and regulate self-destruction of the cell (apoptosis).

CTSD gene mutations that cause congenital NCL lead to a complete lack of cathepsin D enzyme activity. As a result, proteins and other materials are not broken down properly. In the lysosomes, these materials accumulate into fatty substances called lipopigments. These accumulations occur in cells throughout the body, but neurons are likely particularly vulnerable to damage caused by the abnormal cell materials and the loss of cathepsin D function. Early and widespread cell death in congenital NCL leads to severe signs and symptoms and death in infancy.

Related Gene(s)

Changes in this gene are associated with congenital neuronal ceroid lipofuscinosis.

  • CTSD

How do people inherit congenital 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 congenital neuronal ceroid lipofuscinosis?

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

  • Genetic Testing Registry: Neuronal ceroid lipofuscinosis, congenital (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1864670)

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

You may find the following resources about congenital 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 congenital neuronal ceroid lipofuscinosis?

  • cathepsin D deficiency
  • cathepsin D deficient neuronal ceroid lipofuscinosis cathepsin D
  • CLN10
  • neuronal ceroid lipofuscinosis 10
  • neuronal ceroid lipofuscinosis due to cathepsin D deficiency

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 congenital neuronal ceroid lipofuscinosis?

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

What glossary definitions help with understanding congenital neuronal ceroid lipofuscinosis?

apoptosis ; autosomal ; autosomal recessive ; cell ; cerebellum ; cerebral cortex ; ceroid ; congenital ; deficiency ; enzyme ; gene ; inherited ; microcephaly ; nervous system ; recessive ; respiratory ; seizure ; status epilepticus

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

References

  • Fritchie K, Siintola E, Armao D, Lehesjoki AE, Marino T, Powell C, Tennison M, Booker JM, Koch S, Partanen S, Suzuki K, Tyynelä J, Thorne LB. Novel mutation and the first prenatal screening of cathepsin D deficiency (CLN10). Acta Neuropathol. 2009 Feb;117(2):201-8. doi: 10.1007/s00401-008-0426-7. Epub 2008 Sep 2. (http://www.ncbi.nlm.nih.gov/pubmed/18762956?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)
  • Kohlschütter A, Schulz A. Towards understanding the neuronal ceroid lipofuscinoses. Brain Dev. 2009 Aug;31(7):499-502. doi: 10.1016/j.braindev.2008.12.008. Epub 2009 Feb 4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19195801?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)
  • Siintola E, Partanen S, Strömme P, Haapanen A, Haltia M, Maehlen J, Lehesjoki AE, Tyynelä J. Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis. Brain. 2006 Jun;129(Pt 6):1438-45. Epub 2006 May 2. (http://www.ncbi.nlm.nih.gov/pubmed/16670177?dopt=Abstract)
  • Steinfeld R, Reinhardt K, Schreiber K, Hillebrand M, Kraetzner R, Bruck W, Saftig P, Gartner J. Cathepsin D deficiency is associated with a human neurodegenerative disorder. Am J Hum Genet. 2006 Jun;78(6):988-98. Epub 2006 Mar 29. (http://www.ncbi.nlm.nih.gov/pubmed/16685649?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: July 2013
Published: December 16, 2014