The neuronal ceroid-lipofuscinoses

Abstract

The neuronal ceroid lipofuscinoses (NCL) are a relatively frequent group of progressive neurodegenerative disorders in children with similar, but not identical, clinical and morphological features, entailing different clinical groups, some of which have been found to represent different genetic entities, ie, infantile (INCL) or CLN1, late-infantile (LINCL) or CLN2, juvenile (JNCL) or CLN3, and a Finnish variant of LINCL or CLN5. Within the clinical pentad are included seizures, motor disturbances, visual impairment, dementia, and familial occurrence in an autosomal-recessive fashion. The ultrastructure of accruing lipopigments is diagnostically required to recognize an individual patient's NCL by showing granular lipopigments in INCL, curvilinear profiles (with or without fingerprint profiles) in LINCL and fingerprint profiles (with or without curvilinear profiles) in JNCL. Identification of genes for INCL and JNCL, together with electron microscopy in LINCL, allows safe prenatal diagnosis which is still impossible by biochemical techniques, unlike other lysosomal disorders. However, both cause and pathogenesis of the individual forms of NCL are still unknown, and therapy is gravely insufficient.

Btn2, a Hook1 Ortholog and Potential Batten Disease-Related Protein, Mediates Late Endosome-Golgi Protein Sorting in Yeast

“…BTN1 encodes the yeast ortholog of CLN3 (18,59), a gene known to be mutated in NCL patients (30,31,53). Btn1 has been proposed to play a role in vacuolar pH homeostasis (57) and the import of basic amino acids therein (44), although the mechanism is unknown.…”

“…Batten disease belongs to a family of autosomal recessive disorders called neuronal ceroid lipofuscinoses (NCLs) that lead to progressive neurodegeneration and early death in humans (30,31,54). At the cellular level, these diseases are typified by the abnormal accumulation of autofluorescent storage material in the lysosome, followed by subsequent neuron loss.…”

“…At the cellular level, these diseases are typified by the abnormal accumulation of autofluorescent storage material in the lysosome, followed by subsequent neuron loss. The human CLN3 gene, which undergoes mutations that lead to juvenile-onset NCL (JNCL) (30,31,54), has a yeast ortholog called BTN1 (18,59). Importantly, deletion of BTN1 leads to defects in vacuolar pH homeostasis and the up-regulation of BTN2 (12,57), a gene of unclear function involved in cellular adaptation to the loss of BTN1 in yeast and, possibly, the pathogenesis of JNCL in humans.…”

Neuronal Ceroid Lipofuscinosis: A Common Pathway?

“…The NCL share clinical manifestations, biochemistry, and pathology, hence their classification together (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). It is probable that all of the NCL genes belong to a common metabolic pathway (15).…”

Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S.

“…The neuronal ceroid lipofuscinoses (NCLs) 1 are a group of progressive hereditary neurodegenerative disorders of children that are distinguished from other neurodegenerative diseases by the accumulation of autofluorescent material ("aging pigment") in brain and other tissues (reviewed in reference 1). Distinct subgroups of NCL have been recognized that differ in the age of onset of symptoms and the appearance of the storage material by electron microscopy.…”