A form of neuronal ceroid lipofuscinosis associated with pathological genetic mutations in CLN6 and DNAJC5
Neuronal ceroid lipofuscinosis is a neurodegenerative disorder wherein there is an excess of lipofuscin in cells. Lipofuscin is a pigmented lipid granule and a residue of lysosomal digestion. Neuronal ceroid lipofuscinosis is classified into ten types according to the associated gene. Kufs diseaseis a type 4 neuronal ceroid lipofuscinosis and is associated with CLN6 gene (that codes for ceroid-lipofuscinosis neuronal protein 6) and DNAJC5 gene (that codes for cysteine string protein). While other forms of neuronal ceroid lipofuscinosis lead to vision impairment, Kufs disease does not. Nevertheless, it is characterized as well by the accumulation of lipopigments in cells, particularly nerve cells. The accumulation results in the death of the nerve cell, and therefore leads to impairment in brain function.
Kufs disease may be categorized as type A and type B. Type A, in particular, is caused by pathological mutations involving CLN6 and PPT1. The proteins that CLN6 gene codes for are involved in fat transport whereas the enzyme coded by PPT1 is involved in the removal of fatty-acid side chains from the proteins. In type B, the disease is caused by genetic mutations in DNAJC5 and CTSF. DNAJC5 gene is involved in the production of cysteine string protein (involved in signal transmissions through nerves) whereas CTSF gene codes for the enzyme cathepsin F (involved in the breakdown of proteins).
Both types of Kufs disease are hereditary. However, type A is inherited in an autosomal recessive pattern whereas type B is in an autosomal dominant manner.
- adult neuronal ceroid lipofuscinosis (ANCL)
- neuronal ceroid lipofuscinosis type 4