Neuronal Ceroid Lipofuscinoses

This group of lysosomal diseases is distinguished by neuronal storage of glycoproteolipids that resemble ceroid and lipofuscin. Neuronal ceroid lipofuscinosis (NCL) may occur any time from infancy to late adulthood. In children, it is the most common lipid storage disease. The diseases are panethnic, with a worldwide distribution. The mode of inheritance is autosomal recessive. To date, eight mutant genes (CLN1 through CLN8) have been implicated in NCL, and six of them have been identified. The following classification is based on genotype and clinical phenotype correlation:

• The gene CLN1, located on chromosome 1, encodes the lysosomal enzyme palmitoyl protein thioesterase 1 (PPT1). Mutations in the gene result in four pheno-types: infantile, or Haltia-Santavuori disease, late infantile, juvenile, and adult types.

• The gene CLN2, located on chromosome 11, encodes the lysosomal enzyme tripeptidyl peptidase 1 (TPP1).

Mutations in the gene produce the classical late infantile or Jansky-Bielschowsky disease.

• The gene CLN3, located on chromosome 16, encodes a lysosomal membrane protein. Mutations in the gene produce the juvenile or Batten-Vogt-Spielmeyer disease.

• The gene CLN4 is a hypothetical gene for the adult NCL or Kuf disease.

• The genes CLN5 through CLN8 genes are implicated in the Finnish variant, the juvenile variant, and the Northern epilepsy syndrome with mental retardation. The genes encode lysosomal membrane proteins. Two of the proteins (CLN6 and CLN8) are probably localized to the endoplasmic reticulum.

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