Frequency
The prevalence of CLN10 disease is unknown; at least 11 cases have been described.
Causes
Mutations in the CTSD gene cause CLN10 disease. 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 protease enzymes, 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 down certain proteins, turn on (activate) other proteins, and regulate self-destruction of the cell (apoptosis).
CTSD gene mutations found to cause CLN10 disease that is present at birth lead to a complete lack of cathepsin D enzyme activity. As a result, proteins and fats are not broken down properly and abnormally accumulate within lysosomes. While accumulations of these substances occurs in cells throughout the body, nerve cells appear to be particularly vulnerable to damage caused by the abnormal cell materials. Early and widespread loss of nerve cells in CLN10 disease leads to severe signs and symptoms and death in infancy.
In the later-onset cases of CLN10 disease, CTSD gene mutations likely result in the production of a cathepsin D enzyme whose function is greatly reduced but not eliminated. As a result, some proteins and fats are broken down by the enzyme, so it takes longer for these substances to accumulate in lysosomes and cause nerve cell death.
Inheritance
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.
Other Names for This Condition
- Cathepsin D deficiency
- Cathepsin D deficient neuronal ceroid lipofuscinosis
- CLN10
- Congenital neuronal ceroid lipofuscinosis
- Neuronal ceroid lipofuscinosis 10
- Neuronal ceroid lipofuscinosis due to cathepsin D deficiency
Additional Information & Resources
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Clinical Trials
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Anderson GW, Goebel HH, Simonati A. Human pathology in NCL. Biochim Biophys Acta. 2013 Nov;1832(11):1807-26. doi: 10.1016/j.bbadis.2012.11.014. Epub 2012 Nov 29. Citation on PubMed
- 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. Citation on PubMed
- 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. Citation on PubMed
- Siintola E, Partanen S, Stromme P, Haapanen A, Haltia M, Maehlen J, Lehesjoki AE, Tyynela J. Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis. Brain. 2006 Jun;129(Pt 6):1438-45. doi: 10.1093/brain/awl107. Epub 2006 May 2. Citation on PubMed
- 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. doi: 10.1086/504159. Epub 2006 Mar 29. Citation on PubMed or Free article on PubMed Central
- Williams RE, Mole SE. New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology. 2012 Jul 10;79(2):183-91. doi: 10.1212/WNL.0b013e31825f0547. Citation on PubMed
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