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

Reviewed September 2010

What is Kufs disease?

Kufs disease is a condition that primarily affects the nervous system, causing progressive problems with movement and thought (cognition).

Two types of Kufs disease have been described: type A and type B. The two types have different but overlapping signs and symptoms. Type A is characterized by a combination of seizures and uncontrollable muscle jerks (myoclonic epilepsy), a loss of intellectual functions (dementia), impaired muscle coordination (ataxia), involuntary movements (extrapyramidal dysfunction) such as tremors or tics, and speech difficulties (dysarthria). Kufs disease type B is not associated with epilepsy or dysarthria; however, as with Kufs disease type A, its characteristic features include dementia, ataxia, and extrapyramidal dysfunction. Individuals with Kufs disease type B may also experience changes in personality.

The signs and symptoms of Kufs disease typically appear around age 30, but they can develop anytime between adolescence and late adulthood. The condition worsens with time, and affected individuals usually survive about 10 years after the signs and symptoms first begin.

Kufs disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs). These disorders all affect the nervous system and impair movement and cognition. Unlike Kufs syndrome, most other NCLs also cause vision loss.

How common is Kufs disease?

As a group, NCLs affect 2 to 4 per 100,000 newborns worldwide. It is estimated that Kufs disease represents 1.3 to 10 percent of all NCL cases.

What genes are related to Kufs disease?

Mutations in the PPT1 gene can cause Kufs disease. The PPT1 gene provides instructions for making a protein called palmitoyl-protein thioesterase 1. This protein 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 called long-chain fatty acids from other proteins so the fats can be broken down and used for energy.

In people with Kufs disease, a fatty substance called a lipopigment builds up abnormally within the lysosomes of nerve cells (neurons). The buildup of this substance is thought to be harmful to neurons and may ultimately cause these cells to die. Over time, the progressive death of neurons in the brain leads to movement problems and cognitive decline in affected individuals. It is unclear how PPT1 gene mutations relate to lipopigment formation or why the buildup of lipopigment seems to occur only in neurons in people with Kufs disease.

Researchers have identified PPT1 gene mutations in only a few people with Kufs disease. The cause of the majority of cases is unknown. Researchers suspect that other unidentified genes, possibly genes that cause other types of NCL, may be responsible for the disorder in these cases.

Related Gene(s)

Changes in this gene are associated with Kufs disease.

  • PPT1

How do people inherit Kufs disease?

When Kufs disease is caused by mutations in the PPT1 gene, it 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.

Less commonly, Kufs disease can have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. No genes have been found to be associated with autosomal dominant Kufs disease. Most cases 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)

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.

  • MedlinePlus - Health information

    • Encyclopedia: Movement--Uncoordinated (http://www.nlm.nih.gov/medlineplus/ency/article/003198.htm)
    • Health Topic: Dementia (http://www.nlm.nih.gov/medlineplus/dementia.html)
    • Health Topic: Epilepsy (http://www.nlm.nih.gov/medlineplus/epilepsy.html)
    • Health Topic: Movement Disorders (http://www.nlm.nih.gov/medlineplus/movementdisorders.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/10973/resources/resources/1)

  • Additional NIH Resources - National Institutes of Health

    • National Institute of Neurological Disorders and Stroke: Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page (http://www.ninds.nih.gov/disorders/ataxia/ataxia.htm)
    • National Institute of Neurological Disorders and Stroke: Dementia Information Page (http://www.ninds.nih.gov/disorders/dementias/dementia.htm)
    • National Institute of Neurological Disorders and Stroke: Epilepsy Information Page (http://www.ninds.nih.gov/disorders/epilepsy/epilepsy.htm)

  • Educational resources - Information pages

    • Cleveland Clinic: Epilepsy: Frequently Asked Questions (http://my.clevelandclinic.org/disorders/Epilepsy/hic_Epilepsy_Frequently_Asked_Questions.aspx)
    • Cleveland Clinic: Types of Dementia (http://my.clevelandclinic.org/disorders/Dementia/hic_Types_of_Dementia.aspx)
    • Hide and Seek Foundation (http://hideandseek.org/Diseases.html)
    • Merck Manual Home Edition for Patients and Caregivers: Dementia (http://www.merckmanuals.com/home/brain_spinal_cord_and_nerve_disorders/delirium_and_dementia/dementia.html)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=79262)

  • Patient support - For patients and families

    • Batten Disease Support and Research Association (http://www.bdsra.org/what-is-batten-disease/about-batten-disease/)
    • Family Caregiver Alliance: Dementia (http://www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=569)
    • Hide and Seek Foundation (http://hideandseek.org/Diseases.html)
    • National Organization for Rare Disorders (NORD) (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/349/viewAbstract)
    • University of Kansas Medical Center Resource List: Neurologic Conditions (http://www.kumc.edu/gec/support/neuro-me.html)
    • WE MOVE: Worldwide Education and Awareness for Movement Disorders (http://www.wemove.org/)

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

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1428/)

  • Genetic Testing Registry - Repository of genetic test information

    • 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)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22Kuf%27s%20disease%22%20OR%20%22Neuronal%20Ceroid-Lipofuscinoses%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((kufs%20disease%5BTIAB%5D)%20OR%20(adult%20neuronal%20ceroid%20lipofuscinosis%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)

  • OMIM - Genetic disorder catalog

    • CEROID LIPOFUSCINOSIS, NEURONAL, 4A, AUTOSOMAL RECESSIVE (http://omim.org/entry/204300)
    • CEROID LIPOFUSCINOSIS, NEURONAL, 4B, AUTOSOMAL DOMINANT (http://omim.org/entry/162350)

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?

acids ; ataxia ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; ceroid ; cognition ; dementia ; dysarthria ; extrapyramidal ; fatty acids ; gene ; inheritance ; involuntary ; nervous system ; pattern of inheritance ; protein ; recessive ; syndrome

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

References

  • 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)
  • 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)

 

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 2010
Published: May 20, 2013