New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses

Abstract

We provide a new classification for the neuronal ceroid lipofuscinoses (NCLs) that takes into account recent genetic and biochemical advances. This was originally developed by an international group with clinical, molecular genetic, biological, and morphologic interests, further revised by a panel of world experts in the NCLs, and is now updated in light of recent research findings. The aim is to provide young people, carers, and professionals with a diagnostic label that is informative, leads to effective clinical management of symptoms and in the future perhaps a cure, as well as aiding basic scientific and clinical research. We suggest that clinicians should aim to provide every child and family with detailed diagnostic information at clinical, biochemical, and genetic levels where possible, which the new classification allows in a gene-led hierarchical manner. The robustness and applicability of this updated new classification have been independently audited in the clinical setting using a series of patients previously diagnosed with NCL according to standard ultrastructural, biochemical, or genetic criteria.

Retinal Degeneration in Mice Deficient in the Lysosomal Membrane Protein CLN7

“…4 Neuronal ceroid lipofuscinoses have been categorized based on the affected gene (CLN1-CLN8; CLN10-CLN14 disease) and the clinical presentation into congenital, infantile, late-infantile, juvenile, and adult phenotypes. 1,5 These fatal lysosomal storage disorders are characterized by the selective damage and loss of neurons in the brain and the retina, neuroinflammation, and the accumulation of autofluorescent ceroid lipopigments, particularly in neurons containing subunit c of mitochondrial ATP synthase (SCMAS) and/or sphingolipid activator proteins (saposin) A and D. 2 Clinically, typical symptoms of patients with NCL include progressive loss of vision, epileptic seizures, psychomotor retardation, and premature death. 6 CLN7 disease, variant late-infantile phenotype (vLINCL; MIM 610951), is caused by mutations in the CLN7/MFSD8 gene, which encodes a polytopic lysosomal membrane protein with putative transporter function.…”

2-Hydroxypropyl-β-cyclodextrin Promotes Transcription Factor EB-mediated Activation of Autophagy

“…Neuronal ceroid lipofuscinoses (NCLs) are a group of more than 12 genetically distinct neurodegenerative lysosomal storage disorders affecting children and young adults (39,40). The hallmark of NCLs is the aberrant intracellular accumulation of autofluorescent ceroid lipopigments due to mutations in genes encoding proteins involved in lysosomal biogenesis and function (41).…”

Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease)

“…This ongoing work, resulting in a deeper understanding of the molecular genetic basis, will provide improved guidance for the accurate and early diagnosis of ANCL. We anticipate that the recently accepted nomenclature for the NCL 34 will be expanded as new genes are identified.…”