Kufs Disease is characterized by neurologic symptoms that may mimic mental illness, movement malfunction, and problems with sight. Kufs Disease is linked to excess accumulations of pigments (lipofuscins) dissolved in fat tissues that are found throughout the central nervous system. Kufs Disease, Batten Disease, Bielchowsky Disease, and Santavuori-Haltia Disease are different forms of the same family of disorders (neuronal ceroid lipofuscinoses [NCL]) that are differentiated by the age of onset. The various forms of this disorder are often extremely difficult to differentiate from other progressive degenerative diseases of the central nervous system.
Kufs Disease is a very rare disorder marked initially by progressive weakness with diminished muscle coordination, seizures, rapid involuntary jerky movements (chorea), and, rarely, blindness. This disorder can be inherited as either a dominant or recessive trait and is usually slowly progressive.
Neurological symptoms of Kufs Disease usually begin after the age of twenty and can resemble mental illness. Confusion, stupor or psychotic behavior may mark the onset, leading to mental retardation and generalized convulsions. These symptoms are due to excess pigment in fat (lipofuscins) that accumulate in the brains of people with Kufs Disease.
People with Kufs Disease may present with a skin disorder involving dryness, roughness and/or scaliness (ichthyosis vulgaris). This condition arises as a result of excess production and/or retention of keratin (a principal component of skin). (For more information, choose “Ichthyosis” as your search term in the Rare Disease Database).
Kufs Disease is an inherited disorder that may involve either recessive (Kufs Disease) or dominant forms (Parry Disease). The recessive form (Kufs Disease) tends to be more serious than the dominant form.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13″ refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait which are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Kufs Disease usually becomes apparent after the age of twenty, whereas Batten Disease begins during early childhood and Jansky-Bielschowsky Disease begins during late childhood. There is an infantile form as well (Santavuori-Haltia Disease). All of these related lipid storage disorders are rare, occurring in an estimated 2-4 cases per 100,000 live births in the United States. The disorder appears to affect persons in Northern Europe (Finland, Sweden) more frequently than in other regions.
Treatment of Kufs Disease is symptomatic and supportive. Genetic counseling may be of benefit for families of affected patients. Service agencies which aid the mentally disabled could also be helpful to the patient and family.
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Dyken PR. Kuf Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:547.
Adams RD, Victor M, Ropper AA. Eds. Principles of Neurology. 6th ed. McGraw-Hill Companies. New York, NY; 1997:957-58, 967.
Menkes JH, Pine Jr JW, et al. Eds. Textbook of Child Neurology. 5th ed. Williams & Wilkins. Baltimore, MD; 1995:111-16.
Weimer JM, Kriscenski-Perry E, Elshatory Y, et al. The neuronal ceroid lipofuscinoses: mutations in different proteins result in similar disease. Neuromolecular Med. 2002;1:111-24.
Sondhi D, Hackett NR, Apblett RL, et al. Feasibility of gene therapy for late neuronal ceroid lipofuscinosis. Arch Neurol. 2001;58:1793-98.
Santavuori P, Vanhanen SL, Autti T. Clinical and neuroradiological diagnostic aspects of neuronal ceroid lipofuscinoses disorders. Eur J Paediatr Neurol. 2001;5 Suppl A:157-61.
Zhong N. Molecular genetic testing for neuronal ceroid lipofuscinoses. Adv Genet. 2001;45:141-58.
Zhong N, Wisniewski KE. Outlook for future treatment. Adv Genet. 2001;45:217-24.
Wisniewski KE, Kida E, Golabek AA, et al. Neuronal ceroid lipofuscinoses: classification and disgnosis. Adv Genet. 2001;45:1-34.
Gardiner RM. The molecular genetic basis of the neuronal ceroid lipofuscinoses. Neurol Sci. 2000;21(3 suppl):S15-19.
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McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 204300: Last Edit Date; 6/14/2001.
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 162350: Last Edit Date; 10/29/1999.
Batten Disease Support & Research Association (BDSRA). Batten Disease Facts and Figures. Last Revised: 1/31/03. 7pp.
Amersham Health. Neuronal ceroid lipofuscinosis. nd. 1p.
Lupofuscinosis Information. Review date: 12/3/2001. 11pp.