What is CLN2 disease?

CLN2 is a genetic disease

CLN2 disease is a rare genetic disorder that affects children.1,2 CLN2 disease is:

  • Named after the CLN2/TPP1 gene, which is mutated (abnormal) in CLN2 disease2
  • One of the most common forms of neuronal ceroid lipofuscinosis (NCL)2
    • NCLs are a group of inherited disorders, which are collectively known as Batten disease3
  • Previously known as late-infantile NCL, meaning that for most children, symptoms begin between the ages of 2 and 42

CLN2 disease is an inherited disease that is passed down through families
Children with CLN2 disease are born with this condition, even though it may take months or years before they start showing signs.2

CLN2 disease is referred to as an autosomal recessive disorder2:

  • Everyone has two copies of the CLN2 gene, also known as TPP1 gene. In people with CLN2 disease, both inherited genes (one from each parent) have mutations2
  • Parents of a child with CLN2 disease have a mutation in one of their CLN2 genes2
  • Parents are carriers of the genetic mutation, which means they are healthy but can pass on the mutation to their children2
  • If both parents carry the mutation and have a child, there is a2
    • 25% chance that the child will inherit both mutations and be affected by CLN2 disease and experience symptoms
    • 50% chance that the child will be healthy, but they will also carry the one mutation for CLN2 disease
    • 25% chance that the child will not carry any mutation for CLN2 disease and will not have CLN2 disease

Diagnosis can be confirmed through genetic testing, which looks for a mutation in a DNA sample collected from the child. CLN2 diagnosis can also be confirmed through enzyme testing, which looks for low levels of the TPP1 enzyme.4

CLN2 disease is a type of lysosomal storage disorder that affects cells in the brain5

There are lysosomes inside every cell. Lysosomes contain enzymes that break down and recycle material in the cell. One of these enzymes is called TPP1.5

The TPP1 enzyme is missing or does not work properly in children with CLN2 disease. When this enzyme isn't working correctly, certain materials build up in the lysosomes of cells, particularly cells in the brain and the eyes.3,6

CLN2 disease is associated with a buildup of materials inside brain cells3,6

CLN2 disease lysosomal storage disorder cell graphic
CLN2 disease lysosomal storage disorder cell graphic

Over time, this buildup is associated with damaging the cells in the brain and the eyes, and they stop functioning normally. As this happens, the symptoms of CLN2 disease (for example, language development delay, seizures, and visual impairment) appear.3

The BDSRA is committed to raising funds for research, providing family support services, enhancing education, raising awareness, and advocating for legislative action. The Australian Chapter of the BDSRA was formed in 1995 by parents of children affected by Batten Disease.

Visit the Batten Disease Support and Research Association (BDSRA) to learn more about CLN2 disease ›

Key sources
  1. Kohlschütter A, Schulz A. CLN2 disease (classic late infantile neuronal ceroid lipofuscinosis). Pediatr Endocrinol Rev. 2016;13(Suppl 1):682-688.
  2. Mole SE, Williams RE. Neuronal ceroid-lipofuscinoses. 2001 Oct 10 [Updated 2013 Aug 1]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews®.
  3. Haltia M. The neuronal ceroid-lipofuscinoses: from past to present. Biochim Biophys Acta. 2006;1762:850-856.
  4. Fietz M, AlSayed M, Burke D, et al. Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis. Mol Genet Metab. 2016;119:160-167.
  5. Mole SE, Williams RE, Goebel HH. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics. 2005;6:107-126.
  6. Schulz A, Kohlschütter A, Mink J, Simonati A, Williams R. NCL diseases–clinical perspectives. Biochim Biophys Acta. 2013;1832:1801-1806.