The ceroid-lipofuscinoses are a group of inherited neurodegenerative diseases of humans and animals characterised by the accumulation of a fluorescent lipopigment in neurons and other cells within the body. Syndromes occurring in dogs are classified, on the basis of the age of onset and, to a lesser degree, the course of the disease, as prepubertal-protracted, early adult acute and adult onset. Clinical signs are generally those of progressive loss of vision, motor disturbances such as ataxia, tremors, seizures and proprioceptive deficits together with behavioural changes including loss of learned behaviour, fearfulness and aggression. The various syndromes can be expected to reflect different mutations, at least some of which affect the catabolism of subunit c of mitochondrial adenosine triphosphate (ATP) synthase. Confirfnation of diagnosis depends on the demonstration of lipopigment in brain or skin biopsies by histochemistry, fluorescence or electron microscopy.

The severity of neurodegeneration and minor differences in the ultrastructure of storage material implied that this was a different disease from other forms of ovine ceroid-lipofuscinosis that accumulate subunit-c of mitochondrial ATP synthase. An autosomal recessive mode of inheritance is considered probable. Although of only minor economic importance, this disease may be important to research into the group of ceroid-lipofuscinoses as a whole.

Analysis of storage bodies in the ceroid-lipofuscinoses (Batten disease) has demonstrated a high protein content suggestive of a proteinosis. Direct N-terminal sequencing has shown that subunit c of mitochondrial ATP synthase is specifically stored in the disease in sheep and cattle, and in the human late infantile and juvenile diseases, as well as in 3 breeds of dogs. No differences have been found between the stored subunit c and that in normal mitochondria. No other mitochondrial components are stored. Different proteins, sphingolipid activator proteins (SAPs or saposins) A and D, are stored in the infantile disease. Linkage studies have shown that different forms of ceroid-lipofuscinosis are coded for on different genes on different chromosomes. The genes for subunit c, its production, its insertion into mitochondria, and mitochondrial function are normal. This suggests that underlying the various forms of the disease is a family of lesions in the normal pathway of subunit c turnover, after its normal insertion into the ATP synthase complex. Antibodies to subunit c offer one way of mapping that pathway and detecting the sites of lesions. Specific antibodies have been raised against stored subunit c, using a liposomal adjuvant system which proved superior to classical adjuvants. These antibodies are also useful diagnostically, both in Western blotting and in immunocytochemistry.

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