{"id":44,"date":"2026-05-07T10:46:36","date_gmt":"2026-05-07T10:46:36","guid":{"rendered":"https:\/\/hcp.biomarin.com\/en-us\/cln2\/?page_id=44"},"modified":"2026-09-15T14:38:26","modified_gmt":"2026-09-15T14:38:26","slug":"natural-history","status":"publish","type":"page","link":"https:\/\/hcp.biomarin.com\/en-us\/cln2\/overview\/natural-history\/","title":{"rendered":"Natural History"},"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

Natural History\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 follows a devastatingly rapid course\u2014symptoms and irreversible functional loss compound with age<\/h2>\n

Timeline of classic CLN2 disease symptom onset and loss of function1-6<\/sup><\/h4>\n\n\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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Age ranges depicted are averages for the classic late-infantile phenotype. Atypical phenotypes of CLN2 disease can vary in age of onset, rate of progression, and disease manifestation.<\/p>\n<\/figcaption>\n <\/figure>\n <\/div>\n <\/div>\n<\/div>\n\n

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Ages 0 to 2\n<\/h3>\n
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  • Lysosomal accumulation of lipopigments likely begins in the prenatal period, yet children appear to develop normally until the onset of presenting symptoms1<\/sup><\/li>\n
  • The first symptom in a majority of cases is early language delay, as shown in recent clinical findings7<\/sup><\/li>\n
  • In a minority of cases, other developmental delays, motor difficulties, or ataxia may be the first sign4,5<\/sup>\n
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    • Often these can occur together with language delay<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n <\/div>\n<\/div>\n\n
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      Ages 2 to 4 \n<\/h3>\n
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      • Even though language delay may appear earlier, seizures (which occur around age 3) are the symptom that most often leads parents to seek medical attention for CLN2 disease2,8<\/sup><\/li>\n
      • Multiple types of seizures can be observed, including generalized tonic-\u00adclonic, absence, myoclonic, atonic, clonic, and tonic2,4<\/sup>\n
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        • Although seizures are most often unprovoked, febrile seizures may occur4<\/sup><\/li>\n<\/ul>\n<\/li>\n
        • Onset of ataxia often occurs during this stage of the disease5<\/sup><\/li>\n<\/ul>\n <\/div>\n<\/div>\n\n
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          Ages 4 to 7\n<\/h3>\n
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          • Symptoms compound with age, and there is a dramatic loss of previously attained skills. During this age range, children with CLN2 disease typically experience1,2,8,9<\/sup>:\n
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            • Language regression<\/li>\n
            • Myoclonic seizures, both epileptic and nonepileptic<\/li>\n
            • Severe motor function impairment with eventual loss of voluntary movements<\/li>\n
            • Movement disorders such as myoclonus, spasticity, dystonia, and chorea<\/li>\n
            • Visual deterioration which leads to blindness by age 6 or 7<\/li>\n<\/ul>\n<\/li>\n
            • Eventually, there is a complete loss of language and ambulation, and children become wheelchair-dependent, bedridden, and completely reliant on caretakers2<\/sup><\/li>\n<\/ul>\n <\/div>\n<\/div>\n\n
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              Ages 8 to 12\n<\/h3>\n
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              • CLN2 disease is characterized by premature death and the majority of children rarely survive past early adolescence1<\/sup><\/li>\n<\/ul>\n <\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n
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                Blindness is an early symptom in other NCLs, but occurs in the later stage of CLN2 disease.6,9<\/sup><\/strong><\/p>\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n

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                The CLN2 Disease Clinical Rating Scale is an efficient way to assess disease progression in 2 of 4 major functional areas: motor and language ability<\/h2>\n

                The standardized scoring system can be used to quantitatively assess disease progression at diagnosis<\/em> and track loss of function over time<\/em>6<\/sup><\/p>\n

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                • Each functional area is scored on a scale of 3 (grossly normal) to 0 (profoundly impaired)6<\/sup><\/li>\n
                • The highest possible score when assessing motor and language function is 67<\/sup><\/li>\n<\/ul>\n

                  Functional performance ability is rated as follows6<\/sup>:<\/h4>\n\n\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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                  In addition to motor and language function assessments, there are also functional domains (each with a 3\u00ad-point scale) to assess vision and the frequency of seizures.6
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                  \n*In some children, normal motor and\/or language development was never present. In such cases, the best performance achieved by the child was considered normal. When that performance level became recognizably worse, the child was rated a 2 for slightly abnormal motor function and\/or language development.<\/small><\/p>\n\n\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n

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                  CLN2 disease is a race against time<\/h4>\n

                  The majority of children with CLN2 disease experience a consistent loss of motor and language function, as measured by the CLN2 Disease Clinical Rating Scale7<\/sup><\/strong><\/p>\n\n\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n

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                  Longitudinal data from 41 subjects with CLN2 disease in DEM-CHILD registry. CI, confidence interval.<\/p>\n<\/figcaption>\n <\/figure>\n <\/div>\n <\/div>\n<\/div>\n\n

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                  With a rapid rate of progression, 2 years to diagnosis is too long.\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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                  • Average age of first seizure: ~3 years<\/li>\n
                  • Average age of CLN2 disease diagnosis: ~5 years<\/li>\n
                  • Average loss per year: ~2 points<\/li>\n
                  • Median age of death: 10.0 years<\/li>\n<\/ul>\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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                    References:\n<\/h4>\n\t\t\t\t\t\t
                      \n
                    1. 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
                    2. 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
                    3. Schulz A, Kohlsch\u00fctter A, Mink J, Simonati A, Williams R. NCL diseases \u2013 clinical perspectives. Biochimica et Biophysica Acta<\/em>. 2013;1832:1801\u20131806.\n<\/span><\/li>\n
                    4. 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.<\/em> 2013;28:470-478.\n<\/span><\/li>\n
                    5. Worgall S, Sondhi D, Hackett NR, et al. Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA. Hum Gene Ther<\/em>. 2008;19:463-474.\n<\/span><\/li>\n
                    6. 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
                    7. 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
                    8. Schulz A, Ajayi T, Specchio N, et al. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J Med.<\/em> 2018;378:1898-1907\n<\/span><\/li>\n
                    9. 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 <\/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-44","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"\nCLN2 Connection | Natural History | HCP BioMarinBMRN CLN2 DSE HCP EN-US<\/title>\n<meta name=\"description\" content=\"Explore the natural history of CLN2 disease, including typical disease progression, key clinical milestones and the impact on patients over time.\" \/>\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\/natural-history\/\" \/>\n<meta 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