Human pathology in NCL

Abstract

In childhood the neuronal ceroid lipofuscinoses (NCL) are the most frequent lysosomal diseases and the most frequent neurodegenerative diseases but, in adulthood, they represent a small fraction among the neurodegenerative diseases. Their morphology is marked by: (i) loss of neurons, foremost in the cerebral and cerebellar cortices resulting in cerebral and cerebellar atrophy; (ii) an almost ubiquitous accumulation of lipopigments in nerve cells, but also in extracerebral tissues. Loss of cortical neurons is selective, indiscriminate depletion in early childhood forms occurring only at an advanced stage, whereas loss of neurons in subcortical grey-matter regions has not been quantitatively documented. Among the fourteen different forms of NCL described to date, CLN1 and CLN10 are marked by granular lipopigments, CLN2 by curvilinear profiles (CVPs), CLN3 by fingerprint profiles (FPPs), and other forms by a combination of these features. Among extracerebral tissues, lymphocytes, skin, rectum, skeletal muscle and, occasionally, conjunctiva are possible guiding targets for diagnostic identification, the precise type of NCL then requiring molecular analysis within the clinical and morphological context. Autosomal-recessive adult NCL has been linked molecularly to different childhood forms, i.e. CLN1, CLN5, and CLN6, whilst autosomal-dominant adult NCL, now designated as CLN4, is caused by a newly identified separate gene, DNAJC5. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.

Keywords: ADANCL; ANCL; Brain; CNS; CTSD; CVP(s); CVS; Curvilinear; EM; EP; EPMR; ER; ERG; Electron microscopy; Extracerebral tissues; FPP(s); Fingerprint; GROD(s); Granular osmiophilic deposits; JNCL; LFB; LINCL; LM; MPS IIIA; NCL; PAS; PME; PPT1; RLP(s); SAP(s); SCMAS; TPP1; adult-onset NCL; autosomal-dominant adult NCL; central nervous system; chorion villus sample; curvilinear profile(s); electroretinogram; endoplasmic reticulum; evoked potentials; fingerprint profile(s); gene encoding cathepsin D; granular osmiophilic deposit(s); juvenile NCL; late-infantile NCL; light microscopy; luxol fast blue; mucopolysaccharidosis IIIA; neuronal ceroid lipofuscinosis; palmitoyl protein thioesterase 1; periodic acid-Schiff; progressive epilepsy with mental retardation; progressive myoclonus epilepsy; rectilinear profile(s); sphingolipid activator protein(s); subunit C of mitochondrial ATP synthase; transmission electron microscopy; tripeptidyl peptidase 1; vLINCL; variant late-infantile NCL.