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Genetics Home Reference: your guide to understanding genetic conditions
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Kufs disease

Reviewed September 2013

What is Kufs disease?

Kufs disease is a condition that primarily affects the nervous system, causing problems with movement and intellectual function that worsen over time. The signs and symptoms of Kufs disease typically appear around age 30, but they can develop anytime between adolescence and late adulthood.

Two types of Kufs disease have been described: type A and type B. The two types are differentiated by their genetic cause, pattern of inheritance, and certain signs and symptoms. Type A is characterized by a combination of seizures and uncontrollable muscle jerks (myoclonic epilepsy), a decline in intellectual function (dementia), impaired muscle coordination (ataxia), involuntary movements such as tremors or tics, and speech difficulties (dysarthria). Kufs disease type B shares many features with type A, but it is distinguished by changes in personality and is not associated with myoclonic epilepsy or dysarthria.

The signs and symptoms of Kufs disease worsen over time, and affected individuals usually survive about 15 years after the disorder begins.

Kufs disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which are also known as Batten disease. These disorders affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. Kufs disease, however, does not affect vision. The different types of NCLs are distinguished by the age at which signs and symptoms first appear.

How common is Kufs disease?

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 have the condition. Kufs disease is thought to represent 1.3 to 10 percent of all NCLs.

What genes are related to Kufs disease?

Mutations in the CLN6 or PPT1 gene cause Kufs disease type A, and mutations in the DNAJC5 or CTSF gene cause Kufs disease type B. Most of the proteins or enzymes produced from these genes are involved in breaking down proteins or clearing unneeded materials from cells.

The CLN6 gene provides instructions for making a protein that likely regulates the transport of certain proteins and fats within the cell. Based on this function, the CLN6 protein appears to help in the process of ridding cells of materials they no longer need.

The PPT1 gene provides instructions for making an enzyme called palmitoyl-protein thioesterase 1. This enzyme is found in structures called lysosomes, which are compartments within cells that break down and recycle different types of molecules. Palmitoyl-protein thioesterase 1 removes certain fats from proteins, which probably helps break down the proteins.

The protein produced from the DNAJC5 gene is called cysteine string protein alpha (CSPα). This protein is found in the brain and plays a role in the transmission of nerve impulses by ensuring that nerve cells receive signals.

The enzyme produced from the CTSF gene is called cathepsin F. Cathepsin F acts as a protease, which modifies proteins by cutting them apart. Cathepsin F is found in many types of cells and is active in lysosomes. By cutting proteins apart, cathepsin F can break proteins down, turn on (activate) proteins, and regulate self-destruction of the cell (apoptosis).

Mutations in the CLN6, PPT1, DNAJC5, or CTSF gene usually reduce the activity of the gene or impair the function of the protein or enzyme produced from the gene. In many cases, these mutations cause incomplete breakdown of certain proteins and other materials. These materials accumulate in the lysosome, forming fatty substances called lipopigments. In other cases, it is unclear what causes the buildup of lipopigments. In Kufs disease, these accumulations occur in nerve cells (neurons) in the brain, resulting in cell dysfunction and eventually cell death. The progressive death of neurons leads to the signs and symptoms of Kufs disease.

Some people with either type of Kufs disease do not have an identified mutation in any of these four genes. In these individuals, the cause of the condition is unknown.

Related Gene(s)

Changes in these genes are associated with Kufs disease.

  • CLN6
  • CTSF
  • DNAJC5
  • PPT1

How do people inherit Kufs disease?

Kufs disease type A, caused by mutations in the CLN6 or PPT1 gene, has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance 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.

Kufs disease type B, caused by mutations in the DNAJC5 or CTSF gene, has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of Kufs disease type B occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of Kufs disease?

These resources address the diagnosis or management of Kufs disease and may include treatment providers.

  • Gene Review: Neuronal Ceroid-Lipofuscinoses (http://www.ncbi.nlm.nih.gov/books/NBK1428/)
  • Genetic Testing Registry: Adult neuronal ceroid lipofuscinosis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0022797)
  • Genetic Testing Registry: Ceroid lipofuscinosis neuronal 4B autosomal dominant (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1834207)
  • NYU Langone Medical Center (http://www.med.nyu.edu/content?ChunkIID=23620)

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

You may find the following resources about Kufs disease 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 Kufs disease?

  • adult neuronal ceroid lipofuscinosis
  • CLN4A
  • Kuf's disease
  • Kufs type neuronal ceroid lipofuscinosis

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 Kufs disease?

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

What glossary definitions help with understanding Kufs disease?

apoptosis ; ataxia ; autosomal ; autosomal dominant ; autosomal recessive ; breakdown ; cell ; ceroid ; cysteine ; dementia ; dysarthria ; enzyme ; epilepsy ; gene ; inheritance ; involuntary ; lysosome ; mutation ; nervous system ; pattern of inheritance ; protease ; protein ; recessive

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

References

  • Arsov T, Smith KR, Damiano J, Franceschetti S, Canafoglia L, Bromhead CJ, Andermann E, Vears DF, Cossette P, Rajagopalan S, McDougall A, Sofia V, Farrell M, Aguglia U, Zini A, Meletti S, Morbin M, Mullen S, Andermann F, Mole SE, Bahlo M, Berkovic SF. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. Am J Hum Genet. 2011 May 13;88(5):566-73. doi: 10.1016/j.ajhg.2011.04.004. Epub 2011 May 5. (http://www.ncbi.nlm.nih.gov/pubmed/21549341?dopt=Abstract)
  • Josephson SA, Schmidt RE, Millsap P, McManus DQ, Morris JC. Autosomal dominant Kufs' disease: a cause of early onset dementia. J Neurol Sci. 2001 Jul 15;188(1-2):51-60. (http://www.ncbi.nlm.nih.gov/pubmed/11489285?dopt=Abstract)
  • Nijssen PC, Brusse E, Leyten AC, Martin JJ, Teepen JL, Roos RA. Autosomal dominant adult neuronal ceroid lipofuscinosis: parkinsonism due to both striatal and nigral dysfunction. Mov Disord. 2002 May;17(3):482-7. (http://www.ncbi.nlm.nih.gov/pubmed/12112194?dopt=Abstract)
  • Ramadan H, Al-Din AS, Ismail A, Balen F, Varma A, Twomey A, Watts R, Jackson M, Anderson G, Green E, Mole SE. Adult neuronal ceroid lipofuscinosis caused by deficiency in palmitoyl protein thioesterase 1. Neurology. 2007 Jan 30;68(5):387-8. (http://www.ncbi.nlm.nih.gov/pubmed/17261688?dopt=Abstract)
  • Sadzot B, Reznik M, Arrese-Estrada JE, Franck G. Familial Kufs' disease presenting as a progressive myoclonic epilepsy. J Neurol. 2000 Jun;247(6):447-54. (http://www.ncbi.nlm.nih.gov/pubmed/10929274?dopt=Abstract)
  • Smith KR, Dahl HH, Canafoglia L, Andermann E, Damiano J, Morbin M, Bruni AC, Giaccone G, Cossette P, Saftig P, Grötzinger J, Schwake M, Andermann F, Staropoli JF, Sims KB, Mole SE, Franceschetti S, Alexander NA, Cooper JD, Chapman HA, Carpenter S, Berkovic SF, Bahlo M. Cathepsin F mutations cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis. Hum Mol Genet. 2013 Apr 1;22(7):1417-23. doi: 10.1093/hmg/dds558. Epub 2013 Jan 7. (http://www.ncbi.nlm.nih.gov/pubmed/23297359?dopt=Abstract)
  • Velinov M, Dolzhanskaya N, Gonzalez M, Powell E, Konidari I, Hulme W, Staropoli JF, Xin W, Wen GY, Barone R, Coppel SH, Sims K, Brown WT, Züchner S. Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families. PLoS One. 2012;7(1):e29729. doi: 10.1371/journal.pone.0029729. Epub 2012 Jan 3. Erratum in: PLoS One. 2012;7(9). doi:10.1371/annotation/26d7eb64-ccd2-41db-b1aa-7cdc8c1eff95. (http://www.ncbi.nlm.nih.gov/pubmed/22235333?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: September 2013
Published: July 21, 2014