PPT1

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.

Palmitoyl-protein thioesterase 1 is thought to be involved in a variety of cell functions. These functions include transporting materials from the cell surface into the cell (endocytosis), the movement of small sac-like structures called vesicles that transport certain substances within cells (vesicle trafficking), and the self-destruction of cells (apoptosis). Palmitoyl-protein thioesterase 1 is also thought to play a role in the functioning of synapses, which are the connections between nerve cells (neurons) where cell-to-cell communication occurs.

Kufs disease - caused by mutations in the PPT1 gene

At least three mutations in the PPT1 gene have been found to cause Kufs disease. These mutations change single protein building blocks (amino acids) or create a premature stop signal in the instructions used to make palmitoyl-protein thioesterase 1. The PPT1 gene mutations that cause Kufs disease are thought to allow some functional protein to be produced. The small amount of functional protein likely accounts for the development of signs and symptoms later in life, usually around age 30. However, it is unclear how PPT1 gene mutations cause the movement problems and cognitive decline characteristic of Kufs disease.

other disorders - caused by mutations in the PPT1 gene

Mutations in the PPT1 gene are responsible for some neuronal ceroid lipofuscinoses (NCLs), a group of diseases that includes Kufs disease. The features of NCLs include a loss of intellectual functions (dementia), seizures, movement disorders, and progressive vision loss. A fatty substance called a lipopigment builds up in the cells of many affected individuals. The buildup of this substance is thought to damage cells and may ultimately cause cell death, contributing to the signs and symptoms of NCLs.

In addition to Kufs disease, mutations in the PPT1 gene cause the infantile, late-infantile, and juvenile types of NCL. These conditions are differentiated by the age at which signs and symptoms first appear: the infantile form of NCL appears between ages six months and two years, the late infantile form appears between ages two and four, and the juvenile form appears between ages five and nine. Researchers believe that PPT1 gene mutations that allow more functional palmitoyl-protein thioesterase 1 to be produced result in later appearance of the features of NCL. For example, PPT1 gene mutations that cause infantile NCL result in a nearly complete loss of palmitoyl-protein thioesterase 1 activity, while mutations responsible for the juvenile form of the disorder result in a protein that is partially active.

PPT1 gene mutations account for all known cases of infantile NCL; more than 25 mutations have been identified. Mutations in the PPT1 gene are responsible for a small proportion of cases of late infantile NCL and juvenile NCL.