PPT1-related neuronal ceroid lipofuscinosis

What is PPT1-related Neuronal Ceroid Lipofuscinosis?

PPT1-related neuronal ceroid-lipofuscinosis (NCL) is an inherited disease that causes degeneration of the brain leading to a progressive loss of mental and motor skills. It can also cause blindness, and typically leads to an early death. In the final stages of the disease, affected individuals will be motionless and in a vegetative state.

There are several forms of NCL, largely differentiated by the gene responsible and the age at which symptoms begin. Mutations in the PPT1 gene typically result in the infantile or juvenile form of NCL.

Infantile Form

The infantile form of NCL (INCL) usually begins to cause noticeable symptoms between the ages of 6 months and 24 months. Initially, infants will show developmental delays and experience seizures or jerking movements. Often these infants will have small heads. Blindness and seizures will be present by 24 months, after which mental functions will deteriorate. The child’s movement will become spastic and uncontrolled and he or she will develop dementia.

Juvenile Form

The symptoms of juvenile NCL (JNCL), also called Batten disease, often begin between the ages of 4 and 10. These children rapidly lose their vision, which is often the first noticeable symptom. They typically become completely blind within two years. People with JNCL often develop periodic seizures between the ages of 5 and 18.

Between the ages of 8 and 14, mental functions typically decline. Children may have difficulty with speech and show behavioral problems. Some people with JNCL also develop psychiatric problems including disturbed thoughts, attention problems, and aggression. These problems can eventually progress to dementia.

People with JNCL also show a decline in motor function and may have difficulty controlling their own movement.

How common is PPT1-related Neuronal Ceroid Lipofuscinosis?

Approximately 1 in 25,000 people globally are affected by some form of NCL. These diseases are most common in Scandinavian countries, but occur elsewhere as well. In the United States, an estimated 25,000 families are affected by some form of NCL. A subset of all NCLs are caused by mutations in the PPT1 gene. The remainder are caused by mutations in multiple other genes.

INCL is most common in Finland, where 1 in 20,000 births is affected by the disease and 1 in 70 people is a carrier. About half the world's cases of INCL are in Finland. Although many genes may be associated with various forms of NCLs, mutations in the PPT1 gene are frequently seen among the Finnish population.

In Iceland, 7 in 100,000 births are affected by JNCL. Other countries experience fewer cases of JNCL. One study showed 0.7 cases per 100,000 births in Germany.

Exactly how many cases of NCL are caused by mutations in the PPT1 gene is unknown.

How is PPT1-related Neuronal Ceroid Lipofuscinosis treated?

There is no treatment for the underlying cause of NCL. Treatments can only address the symptoms as they arise. Various medications can be useful for treating seizures, poor muscle tone, sleep disorders, mood disorders, excessive drooling, and digestion. In some people, a feeding tube is also helpful.

What is the prognosis for a person with PPT1-related Neuronal Ceroid Lipofuscinosis?

The prognosis for a person with NCL depends upon the type of the disease he or she has. People with INCL or JNCL will become blind and will deteriorate mentally. They will eventually enter a vegetative state and become totally dependent on others to care for them.

Among those with INCL, death usually occurs in childhood.

Among those with JNCL, death usually occurs between one's late teens to 30s.