Batten disease (juvenile-onset neuronal ceroid lipofuscinosis [JNCL]) is an autosomal recessive condition characterized by accumulation of lipopigments (lipofuscin and ceroid) in neurons and other cell types.
Juvenile neuronal ceroid lipofuscinosis (JNCL) is a lysosomal storage disease caused by autosomal recessive mutations in ceroid lipofuscinosis 3 (CLN3).
The purpose of this study was to compare the in vivo 1.5-T 1H magnetic resonance (MR) and ex vivo 14.3-T high-resolution (HR) magic angle spinning (MAS) 1H MR brain spectra of patients with infantile (CLN1) and juvenile (CLN3) types of NCL, to obtain detailed information about the alterations in the neuronal metabolite profiles in these diseases and to test the suitability of the ex vivo HR MAS (1)H MRS technique in analysis of autopsy brain tissue.
Classic late-infantile NCL (Jansky-Bielschowsky disease) is caused by mutations in a gene encoding a pepstatin-insensitive lysosomal peptidase (CLN2 on chromosome 11p15), and juvenile-onset NCL (Batten disease) is caused by mutations in a gene encoding a 438-amino-acid membrane protein (CLN3 on chromosome 16p12) of unknown function.
The juvenile form of the disease (onset age 4-8 years with visual loss) is usually caused by mutations in the CLN3 gene, but some cases have been shown to be due to specific mutations in the CLN1 or CLN2 genes, which are usually associated with NCL with onset in infancy or late infancy, respectively.
Material includes 159 probands with NCL (37 CLNI, 72 classical CLN2, 10 variant LINCL, and 40 CLN3) collected at the New York State Institute for Basic Research in Developmental Disabilities (IBR) as well as a comprehensive review of the literature.
Although the CLN3 gene associated with the disease process in subjects with the juvenile form of neuronal ceroid lipofuscinosis was discovered in 1995, our knowledge of the physiological function of its gene product, CLN3 protein, is still incomplete.
CLN3 is an endosomal/lysosomal transmembrane protein mutated in classical juvenile onset neuronal ceroid lipofuscinosis, a fatal inherited neurodegenerative lysosomal storage disorder.
In this family, the patient and one of the healthy siblings have identical haplotypes, excluding linkage of early juvenile NCL to the CLN3 locus on 16p12.1-11.2.
Using a metabolomics approach based on high resolution 1H NMR spectroscopy of the cortex, cerebellum, and remaining regions of the brain in conjunction with statistical pattern recognition, we report metabolic deficits associated with juvenile NCL in a Cln3 knock-out mouse model.
Juvenile neuronal ceroid-lipofuscinosis is the most common type of neuronal ceroid-lipofuscinosis in the United States and Europe and is inherited as an autosomal recessive genetic disorder.