Neuronal Ceroid Lipofuscinoses

The neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative disorders. Batten disease is the term applied to the juvenile form of NCL, although some physicians use the term to describe all forms of NCLs. The NCLs are characterized by a buildup of pigments called lipofuscins in the body’s cells.

Neuronal ceroid lipofuscinoses affect both males and females, and people of all ethnic backgrounds, although a higher prevalence of NCL has been reported in Scandinavian countries, especially Finland. Worldwide estimates of NCL are about 1 individual per 20,000-100,000 people.

Types of neuronal ceroid lipofuscinosis and symptoms
In general, the NCLs are defined by their age of onset and symptoms.

• Infantile NCL (Santavuori-Haltia disease) – symptoms begin between ages 6 and 24 months. Initial symptoms are clumsiness, low muscle tone (hypotonia), and irritability. Over time, seizures, loss of muscle coordination (ataxia), dementia, and very severe wasting away of brain tissue (cerebral atrophy) occur. Children with this form of NCL have a life expectancy of 5 to 10 years. Infantile NCL is associated with the CLN1 gene.
• Late infantile NCL (Jansky-Bielschowsky type) – symptoms begin between ages 2 and 4 years. Initial symptoms are seizures and ataxia. Over time, cerebral atrophy and dementia occur. Children with this form of NCL have a life expectancy of 8 to 12 years. Late infantile NCL is associated with the CLN2 gene, as well as mutations in the CLN5, CLN6, and CLN7 genes.
• Juvenile NCL (Batten disease) (Spielmeyer-Sjogren type) – symptoms begin between ages 5 and 8 years. Initial symptoms are visual loss or seizures. Over time, ataxia, moderate cerebral atrophy, and dementia occur. Individuals with this form of NCL have a life expectancy of 20s–40s. Juvenile NCL is associated with the CLN3 gene.
• Adult NCL (Kufs disease or Parry disease) – symptoms begin before age 40 years. Symptoms are milder and progress slowly. Dementia and moderate cerebral and cerebellar atrophy occur. Age of death is variable but generally there is a shortened life expectancy. Adult NCL is associated with the CLN4 gene.
• Progressive epilepsy with mental retardation (PEMR) – symptoms (seizures) begin between ages 5 and 8 years. Over time, cognitive loss occurs. Individuals with PEMR generally have a normal life expectancy. PEMR is associated with the CLN8 gene.

In addition, more than 15 other types of NCL have been described, including variant infantile, early juvenile, late juvenile, and protracted juvenile.

Diagnosis
Neuronal ceroid lipofuscinoses are diagnosed based on the symptoms the child or young adult is experiencing. In addition, diagnostic tests such as electroencephalogram (EEG, to look for seizure activity) and magnetic resonance imaging (MRI, to look for changes in the brain) may be done. Samples of skin or tissue may be examined under a microscope to look for the buildup of lipofuscins. Eye tests may be done to look for various eye problems that occur in childhood NCLs.

Treatment
No specific treatment is yet available to cure or slow the progression of neuronal ceroid lipofuscinosis. Seizures can be controlled with antiseizure medications, and other medical problems can be treated as needed. Support groups such as the Hide and Seek Foundation For Lysosomal Research provide support and information on treatments for NCLs and research.

Last update 2/16/06

Information for this article was taken from:
- Chang, C. H. (2002). Neuronal ceroid lipofuscinoses. eMedicine, accessed at http://www.emedicine.com/neuro/topic498.htm
- National Institute of Neurological Disorders and Stroke. What is Batten disease?