{"id":40,"date":"2026-05-07T10:45:53","date_gmt":"2026-05-07T10:45:53","guid":{"rendered":"https:\/\/hcp.biomarin.com\/en-us\/cln2\/?page_id=40"},"modified":"2026-09-15T14:36:31","modified_gmt":"2026-09-15T14:36:31","slug":"cln2-disease","status":"publish","type":"page","link":"https:\/\/hcp.biomarin.com\/en-us\/cln2\/overview\/cln2-disease\/","title":{"rendered":"CLN2 Disease"},"content":{"rendered":"
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\n\t\t\t\t\t\t\t\t Overview<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t

CLN2 Disease\n<\/h1>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n
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CLN2 disease is a rare and rapidly progressing pediatric neurodegenerative genetic disorder1,2<\/sup><\/h2>\n\n\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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CLN2 disease:<\/h4>\n
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  • Is an autosomal recessive lysosomal storage disorder (LSD)2<\/sup><\/li>\n
  • Is one of the most common forms of neuronal ceroid lipofuscinosis (NCL)2<\/sup><\/li>\n
  • Late infantile disease has an estimated incidence of 0.46 per 100,000 live births3<\/sup><\/li>\n
  • Most commonly presents as the late\u2013infantile phenotype4<\/sup><\/li>\n
  • Mutations in the CLN2\/TPP1<\/em> gene, which is located on chromosome 11p15 [63], result in deficient lysosomal activity of tripeptidyl-peptidase 1 (TPP1)4<\/sup><\/li>\n<\/ul>\n\n\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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    CLN2 disease presents both classically and atypically4<\/sup><\/h4>\n

    CLN2 disease, classic phenotype4<\/sup>:<\/strong><\/p>\n

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    • Late\u2013infantile onset\n
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      • The majority of diagnosed cases present with this phenotype and progress in a rapid and predictable manner<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n

        CLN2 disease, atypical phenotype4-5,7-8<\/sup>:<\/strong><\/p>\n

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        • Age of onset, rate of progression, and symptom progression vary, for example:\n
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          • Infantile, with onset under the first year<\/li>\n
          • Late\u2013infantile onset with a protracted progression and patients may live into their 20s<\/li>\n
          • Juvenile onset with a classic progression<\/li>\n<\/ul>\n<\/li>\n
          • Residual TPP1 enzyme activity is more common in atypical CLN2 phenotypes<\/li>\n<\/ul>\n\n\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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            CLN2 disease experts have identified a path to expedite earlier diagnosis in children with CLN2 disease based on probing around early language development9<\/sup><\/h4>\n

            CLN2 disease should be suspected in children aged 2 to 4 with new-onset, unprovoked seizures preceded by early language delay<\/strong><\/p>\n

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            • In CLN2 disease, onset of unprovoked seizures typically occurs between ages 2 and 4; febrile seizures may also occur1,10<\/sup><\/li>\n
            • 83% of children with CLN2 disease experienced delay of early language development11<\/sup><\/li>\n
            • In a minority of cases, other developmental delays or ataxia may be the first sign, though these can often occur along with the language delay5<\/sup><\/li>\n<\/ul>\n\n\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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              Probing on early language development in children who have had seizures can enable earlier diagnosis of CLN2 disease and access to specific care.\n<\/h2>\n \t\t\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n
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              References:\n<\/h4>\n\t\t\t\t\t\t
                \n
              1. Schulz A, Kohlsch\u00fctter A, Mink J, Simonati A, Williams R. NCL diseases\u2013clinical perspectives. Biochimica et Biophysica Acta.<\/em> 2013;1832:1801-1806.\n<\/span><\/li>\n
              2. Malik K, Santucci K, Sremba L, et al. Neuronal Ceroid Lipofuscinoses Overview. 2001 Oct 10 [Updated 2025 May 29]. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026.\n<\/span><\/li>\n
              3. Claussen M, Heim P, Knispel J, Goebel HH, Kohlsch\u00fctter A. Incidence of neuronal ceroid-lipofuscinoses in West Germany: variation of a method for studying autosomal recessive disorders. 1992;42:536-538.\n<\/span><\/li>\n
              4. Mole SE, Williams RE, and Goebel HH. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics.<\/em> 2005;6:107-126.\n<\/span><\/li>\n
              5. Chang M, Cooper JD, Davidson BL, et al. CLN2. In: Mole S, Williams R, and Goebel H, eds. The neuronal ceroid lipofuscinoses (Batten Disease)<\/em>. 2nd ed. Oxford, United Kingdom: Oxford University Press; 2011:80-109.\n<\/span><\/li>\n
              6. Williams RE, Aberg L, Autti T, et al. Diagnosis of the neuronal ceroid lipofuscinoses: an update. Biochimica et Biophysica Acta.<\/em> 2006;1762:865-872.\n<\/span><\/li>\n
              7. Steinfeld R, Heim P, von Gregory H, et al. Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations. Am J Med Genet.<\/em>2002;112:347-354.\n<\/span><\/li>\n
              8. Kousi M, Lehesjoki A-\u00adE, 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-\u00ad63.\n<\/span><\/li>\n
              9. 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.<\/em> 2016 Sep;119(1-2):160-7. doi: 10.1016\/j.ymgme.2016.07.011.\n<\/span><\/li>\n
              10. P\u00e9rez-Poyato MS, Marfa MP, Abizanda IF, et al. Late infantile neuronal ceroid lipofuscinosis: mutations in the CLN2 gene and clinical course in Spanish patients. J Child Neurol. 2013;28:470-478.\n<\/span><\/li>\n
              11. Nickel M, Simonati A, Jacoby D, et al. Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study. Lancet Child Adolesc Health.<\/em> 2018 Aug;2(8):582-590. doi: 10.1016\/S2352-4642(18)30179-2.\n<\/span><\/li>\n <\/ol>\n\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":0,"parent":36,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"class_list":["post-40","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"\nCLN2 Connection | CLN2 Disease | HCP BioMarin<\/title>\n<meta name=\"description\" content=\"Learn about CLN2 disease, a rare pediatric neurodegenerative disorder, including its underlying cause, clinical features and disease progression.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/overview\/cln2-disease\/\" \/>\n<meta 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