Neuronal ceroid lipofuscinsosis (NCL), also known as Batten disease, is a group of neurodegenerative genetic lysosomal storage disorders affecting 1-4 children/100,000 live births, that leads to premature death.
The major characteristic of NCL is an excessive accumulation of autofluorescent ceroid-lipofuscin in neuronal cells or in other cells from patients. These accumulated lipofuscins show a fluorescent greenish-yellow color under a UV microscope.
Because NCL starts with seizures and/or vision failure followed by progressive motor dysfunction and cognitive decline, it is often misdiagnosed as one of the other neurological disorders.
Batten disease presents as seizures and / or vision failure followed by progressive motor dysfunction and cognitive decline.
NCLs are inherited in an autosomal recessive pattern, and their frequencies vary based on genetic mutations and region. Over 400 different mutations are found in 14 different genes so far. Most of the proteins encoded by them are soluble enzymes (CLN1/PPT1, CLN2/TPP1, CLN10/CTSD, SLN13/CTSF) in the lysosome, soluble lysosomal protein (CLN5), and transmembrane proteins (CLN3, CLN6, CLN7/MFSD8, CLN8, CLN12/ATP132A).
Among them, CLN6 and CLN8 localize in the endoplasmic reticulum, while CLN4/DNAJC5 and CLN14/KCTD7 are cytoplasmic and associate with cell membranes. However, most of the physiological substrates of the lysosomal enzymes and functions of the transmembrane proteins are unknown. Such multiple responsible genes and various gene mutations make therapeutic interventions very challenging.
There is no cure for Batten disease at the moment. The standard of care is to minimize symptoms, especially relief from seizures.