NCL diseases — clinical perspectives

Abstract

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders and together are the most common degenerative brain diseases in childhood. They are a group of disorders linked by the characteristic accumulation of abnormal storage material in neurons and other cell types, and a degenerative disease course. All NCLs are characterized by a combination of dementia, epilepsy, and motor decline. For most childhood NCLs, a progressive visual failure is also a core feature. The characteristics of these symptoms can vary and the age at disease onset ranges from birth to young adulthood. Genetic heterogeneity, with fourteen identified NCL genes and wide phenotypic variability render diagnosis difficult. A new NCL classification system based on the affected gene and the age at disease onset allows a precise and practical delineation of an individual patient’s NCL type. A diagnostic algorithm to identify each NCL form is presented here. Precise NCL diagnosis is essential not only for genetic counseling, but also for the optimal delivery of care and information sharing with the family and other caregivers. These aspects are challenging because there are also potential long term complications which are specific to NCL type. Therefore care supported by a specifically experienced team of clinicians is recommended. As the underlying pathophysiological mechanism is still unclear for all NCL forms, the development of curative therapies remains difficult. This article is part of a Special Issue entitled: The neuronal ceroid lipofuscinoses or Batten Disease.

Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations

“…Clinically and neuroradiologically these latter diseases overlap with milder forms of Neuronal Ceroid Lipofuscinosis (NCLs), a group of progressive neurodegenerative disorders characterized by the intralysosomal accumulation in both neural and peripheral tissues of autofluorescent, electron-dense cytoplasmic lipopigments (bearing close resemblance to lipofuscin) [1]. Clinically, NCLs are characterized by a variable combination of visual impairment, cerebellar ataxia, drug-resistant progressive myoclonic epilepsy, behavioral disturbances, mental deterioration, and early death [17].…”

Volumetric Description of Brain Atrophy in Neuronal Ceroid Lipofuscinosis 2: Supratentorial Gray Matter Shows Uniform Disease Progression

“…4 Nonclassic presentations (ie, juvenile, adult, or infantile onset) exist as well. 3,[5][6][7][8] On conventional MR imaging, a marked supratentorial and infratentorial atrophy with ventriculomegaly is the typical finding. In addition, a progressive-but-mild increase of WM signal intensity on T2WI and increased ADC values are observed.…”

Clinical and genetic characteristics and diagnosis of hereditary variants of neonatal epilepsy

“…Среди лизосомных болезней накопления судорож-ный синдром чаще всего возникает при нейрональных цероидных липофусцинозах [14,15]. Это генетически гетерогенная группа болезней, включающая 13 гене-тических вариантов.…”