Severe progressive neurological paediatric disease mucopolysaccharidosis III type C is caused by mutations in the HGSNAT gene leading to deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase involved in the lysosomal catabolism of heparan sulphate. To understand the pathophysiology of the disease we generated a mouse model of mucopolysaccharidosis III type C by germline inactivation of the Hgsnat gene. At 6-8 months mice showed hyperactivity, and reduced anxiety. Cognitive memory decline was detected at 10 months and at 12-13 months mice showed signs of unbalanced hesitant walk and urinary retention. Lysosomal accumulation of heparan sulphate was observed in hepatocytes, splenic sinus endothelium, cerebral microglia, liver Kupffer cells, fibroblasts and pericytes. Starting from 5 months, brain neurons showed enlarged, structurally abnormal mitochondria, impaired mitochondrial energy metabolism, and storage of densely packed autofluorescent material, gangliosides, lysozyme, phosphorylated tau, and amyloid-β. Taken together, our data demonstrate for the first time that deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase causes lysosomal accumulation of heparan sulphate in microglial cells followed by their activation and cytokine release. They also show mitochondrial dysfunction in the neurons and neuronal loss explaining why mucopolysaccharidosis III type C manifests primarily as a neurodegenerative disease.

APOE genotype strongly predicts the rate of cognitive decline in Alzheimer disease. The decline shows a dose-response relation with the APOE epsilon4 allele, but the APOE epsilon2 allele is protective. The nonlinear model yielded larger estimates of the maximal rate of decline than the linear.

We have described the oral status and salivary flow rate of 30 children and adolescents suffering from chronic renal failure (CRF) undergoing hemodialysis and compared the associated parameters with those of 30 clinically healthy subjects with no history of chronic disease. The subjects of the renal group (RG) and healthy group (HG) were paired by gender and age (7-19 years old). Anamneses and an interview consisting of questions on oral hygiene habits comprised the first step in the study, followed by whole and parotid saliva collection and intra-oral examination. No statistical significant difference was found between the RG and HG subjects in terms of the presence of gingival inflammation, dental history of caries, and enamel hypoplasia. However, statistical significant differences were found between the groups related to a sensation of dry mouth, salivary flow rate, delayed tooth eruption, dental staining by iron supplementation, presence of plaque, and dental calculus. Based on our results, we conclude that CRF children and adolescents undergoing hemodialysis present some oral manifestations related to their disease. These manifestations include a sensation of dry mouth, delayed tooth eruption, dental staining by iron supplementation, and dental calculus. A lower flow rate of whole and parotid saliva production just before hemodialysis was also observed.

Tordo et al. present a novel AAV gene therapy vector, AAV-TT, which exceeds the current benchmark neurotropic serotypes AAV9 and AAVrh10 and enables unprecedented correction of a lysosomal transmembrane enzyme deficiency. AAV-TT based gene therapies may thus be suitable for the treatment of human neurological diseases characterised by global neuropathology.