Late-Infantile Neuronal Ceroid-Lipofuscinosis

Markesbery, William R.; Shield, Lloyd K.; Egel, Robert T.; Jameson, H. Douglas

doi:10.1001/archneur.1976.00500090036007

Cited by 32 publications

(2 citation statements)

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“…Classic CLN2 disease demonstrates pure membrane-bound curvilinear profiles, which are a hallmark of the disease [36,42,43]. This specific pattern is not found in any other NCL disorder [36,40,41]. Those with atypical CLN2 disease often have a later onset of symptoms [16,17] and tend to have a mixed pattern of curvilinear storage material and fingerprint stacks seen on electron microscopy of their lymphocytes [40,44,45].…”

Section: Introductionmentioning

confidence: 97%

“…These abnormal inclusions are present in lymphocytes and can only be visualised using electron microscopy since conventional light microscopy lacks the resolution needed to characterise such fine detail [36,40]. Visualisation of curvilinear storage inclusions in peripheral blood samples has circumvented the historical need for more invasive tests such as skin and rectal biopsies and has made it easier to detect cases earlier [41]. Electron microscopy is readily available in centres providing NCL diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2

et al. 2023

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The introduction of intracerebroventricular (ICV) enzyme replacement therapy (ERT) for treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease has produced dramatic improvements in disease management. However, assessments of therapeutic effect for ICV ERT are limited to clinical observational measures, namely the CLN2 Clinical Rating Scale, a subjective measure of motor and language performance. There is a need for an objective biomarker to enable assessments of disease progression and response to treatment. To address this, we investigated whether the proportion of cells with abnormal storage inclusions on electron microscopic examination of peripheral blood buffy coats could act as a biomarker of disease activity in CLN2 disease. We conducted a prospective longitudinal analysis of six patients receiving ICV ERT. We demonstrated a substantial and continuing reduction in the proportion of abnormal cells over the course of treatment, whereas symptomatic scores revealed little or no change over time. Here, we proposed the use of the proportion of cells with abnormal storage as a biomarker of response to therapy in CLN2. In the future, as more tissue-specific biomarkers are developed, the buffy coats may form part of a panel of biomarkers in order to give a more holistic view of a complex disease.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2

et al. 2023

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The Cellular Pathology of Neuronal Ceroid-Lipofuscinosis

Williams¹

1977

Arch Neurol

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A cerebral biopsy specimen from a 4-year-old girl with a moderately advanced stage of the late infantile form of neuronal ceroid-lipofuscinosis was observed in routine cell and fiber stains and in Golgi and electronmicroscopic preparations. There was no evidence of neuronal degeneration or loss. Golgi impregnations identified a fusiform enlargement of proximal axon segments of most pyramidal neurons and some polymorphic neurons but not of other cortical neuronal classes. Typical curvilinear inclusions were found in all cells and appeared to be impacted within the dilated proximal axon segments of pyramidal neurons. The numbers of type II synapses on the axon hillock and dilated proximal axon segments of pyramidal neurons were much reduced, whereas type I synapses remained abundant in the neuropil.

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