NCL Disorders

CLN2 disease is one of the most common forms of NCL, also known as Batten disease1,2

There are 14 known types of neuronal ceroid lipofuscinosis (NCL)3

NCLs are a group of disorders that are the leading cause of dementia in children and adolescents.3

NCL disease nomenclature has recently been revised and reclassified to take into account the mutated gene and clinical onset4

Classification and characteristics of NCLs4-6

*Known NCL diseases. Additional NCL genes remain to be identified.

†SCAR7 is caused by TPP1 deficiency and may be a milder form of CLN2.

CLN2 and CLN3 are the most common forms of NCL worldwide.1

NCLs share a host of etiological and clinical characteristics3

  • Severe and progressive neurodegeneration1
  • Debilitating triad of symptoms—seizures, dementia, and vision loss3
  • Neuronal and retinal accumulation of ceroid lipofuscin7
    • NCLs feature distinct inclusion bodies, including granular, curvilinear, and fingerprint profiles
    • In CLN2, the distinct curvilinear structure of ceroid lipofuscin is evident under microscopy
  • Classic and atypical presentations with varying age of onset, symptoms, and disease course based on type and phenotype3

1. 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® [internet]. Seattle, WA: University of Washington; 1993-2016. 2. Haltia M. The neuronal ceroid-lipofuscinoses: from past to present. Biochimica et Biophysica Acta. 2006;1762:850-856. 3. Schulz A, Kohlschütter A, Mink J, Simonati A, Williams R. NCL diseases – clinical perspectives. Biochimica et Biophysica Acta. 2013;1832:1801-1806. 4. Williams RE, Mole SE. New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology. 2012;79:183-191. 5. Kousi M, Lehesjoki A-­E, Mole SE. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum Mutat. 2012;33:42-­63. 6. 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 Sep;119(1-2):160-7. doi: 10.1016/j.ymgme.2016.07.011. 7. Mole SE, Williams RE, and Goebel HH. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics. 2005;6:107-126.