ArticleActa neuropathologica2008
Atypical CLN2 with later onset and prolonged course: a neuropathologic study showing different sensitivity of neuronal subpopulations to TPP1 deficiency.
Article in Acta neuropathologica, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients.Orphanet journal of rare diseases · 2021Pooled it
- Bi-allelic TPP1 variants in neuronal ceroid lipofuscinosis 2: clinical findings from an Iranian cohort of 20 patients, founder effect, and in silico analyses.Human genetics · 2026Article
- Classic and Atypical Late Infantile Neuronal Ceroid Lipofuscinosis in Latin America: Clinical and Genetic Aspects, and Treatment Outcome with Cerliponase Alfa.Molecular genetics and metabolism reports · 2024Article
- HomozygousGenes · 2024Article
- Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2.Brain sciences · 2023Article
- Visual perception and macular integrity in non-classical CLN2 disease.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2022Observational
- Identification of aJournal of clinical medicine · 2022Article
- Natural History Studies in NCL and Their Expanding Role in Drug Development: Experiences From CLN2 Disease and Relevance for Clinical Trials.Frontiers in neurology · 2022Review
- Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy.Life (Basel, Switzerland) · 2021Article
- An ERG and OCT study of neuronal ceroid lipofuscinosis CLN2 Battens retinopathy.Eye (London, England) · 2021Article
- "Real world effectiveness of cerliponase alfa in classical and atypical patients. A case series".Molecular genetics and metabolism reports · 2021Article
- Cerliponase Alfa for the Treatment of Atypical Phenotypes of CLN2 Disease: A Retrospective Case Series.Journal of child neurology · 2021Article
- Revealing the clinical phenotype of atypical neuronal ceroid lipofuscinosis type 2 disease: Insights from the largest cohort in the world.Journal of paediatrics and child health · 2021Article
- Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease.Human mutation · 2019Article
- High diagnostic yield of direct Sanger sequencing in the diagnosis of neuronal ceroid lipofuscinoses.JIMD reports · 2019Article
- Genetic landscape of pediatric movement disorders and management implications.Neurology. Genetics · 2018Article
- Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study.The Lancet. Child & adolescent health · 2018Observational
- Volumetric Description of Brain Atrophy in Neuronal Ceroid Lipofuscinosis 2: Supratentorial Gray Matter Shows Uniform Disease Progression.AJNR. American journal of neuroradiology · 2016Article
- Article
- Therapeutic approaches to the challenge of neuronal ceroid lipofuscinoses.Current pharmaceutical biotechnology · 2011Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
This is the first neuropathology report of a male patient (born 1960-died 1975) with an extremely rare, atypical variant of CLN2 that has been diagnosed only in five families so far. The clinical history started during his preschool years with relatively mild motor and psychological difficulties, but with normal intellect and vision. Since age six there were progressive cerebellar and extrapyramidal symptomatology, amaurosis, and mental deterioration. Epileptic seizures were absent. The child died aged 15 years in extreme cachexy. Neuropathology revealed neurolysosomal storage of autofluorescent, curvilinear and subunit c of mitochondrial ATP synthase (SCMAS) rich material. The neuronal storage led to laminar neuronal depopulation in the cerebral cortex and to a practically total eradication of the cerebellar cortical neurons. The other areas of the central nervous system including hippocampus, which are usually heavily affected in classical forms of CLN2, displayed either a lesser degree or absence of neuronal storage, or storage without significant neuronal loss. Transformation of the stored material to the spheroid like perikaryal inclusions was rudimentary. The follow-up, after 30 years, showed heterozygous values of TPP1 (tripeptidylpeptidase 1) activity in the white blood cells of both parents and the sister. DNA analysis of CLN2 gene identified a paternal frequent null mutation c.622C > T (p.Arg208 X) in the 6th exon and a maternal novel mutation c.1439 T > G in exon 12 (p.Val480Gly). TPP1 immunohistochemistry using a specific antibody gave negative results in the brain and other organs. Our report supports the notion that the spectrum of CLN2 phenotypes may be surprisingly broad. The study revealed variable sensitivities in neuronal subpopulations to the metabolic defect which may be responsible for the variant's serious course.
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