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.

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.

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.

Read more about the PPT1 gene.

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.