| description |
Neuronal ceroid lipofuscinosis (NCL) is an inherited lysosomal storage disease that has been described in a variety of dog breeds, where it is caused by different mutations. However, the causative gene defect in the Alpine Dachsbracke has not been known so far. Here we present two confirmed cases of NCL from different litters of the same sire with a different dam showing the same underlying gene mutation. Case 1, a 2-year-old male Alpine Dachsbracke was presented with sudden blindness, disorientation, reduction of food intake and character changes such as anxiety states and aggressiveness. Clinical examination revealed moderate obtundation, posttectal blindness and ventral strabism. MRI scans showed dilation of all cerebral ventricles, thinning of the intermediate mass of the thalamus and widening of the cerebral sulci consistent with general cerebral atrophy. Liquor cytology did not reveal any pathological findings. NCL, a hereditary lysosomal storage disease was suspected and confirmed post mortem. Microscopic examination of case 1 revealed granular, eosinophilic, autofluorescent, PAS- and Sudanblack B-positive material in neurons of the central and enteric nervous system as well as in macrophages within spleen, lymphnodes and lung. The storage bodies labelled negative with sphingolipid activator protein D and subunit c of the mitochondrial ATP synthase. Ultrastructurally the material presented as osmiophilic depositions. Case 2, a XX-year old female Alpine Dachsbracke was presented with … Microscopic examination of the brain of case 2 revealed the same granular, eosinophilic, autofluorescent, PAS- and Sudanblack B-positive material in neurons. Whole genome sequencing of the affected dogs revealed a homozygous deletion encompassing the entire CLN8 gene representing the most likely causative mutation for the observed NCL form in both cases. The deletion follows recessive inheritance since the dam and a male littermate of case 1 were tested as heterozygous carriers. This is the first detailed description of CLN8 associated NCL in Alpine Dachsbracke dogs, which provides a novel canine CLN8 model leading to this lysosomal storage disease. |