Ovine ceroid-lipofuscinosis is a proteolipid proteinosis

The pathogenesis of the ceroid-lipofuscinoses, inherited storage diseases of children, was studied in an ovine model. This was shown to have clinical and pathological features most in common with the late infantile and juvenile human forms of the disease. The ability to study sequential changes allowed the retinal lesions to be described as a dystrophy of photoreceptor outer segments which preceded loss of the photoreceptor cells. An early decrease in amplitude of the c-wave electroretinograph was attributed to a decrease in the transpigment epithelial component. The decreased a- and b-wave amplitudes were attributed to the changes in and loss of, photoreceptor cells. The chemical components of isolated storage cytosomes were analyzed and shown to consist mostly of protein. Sequence analysis of the dominantly stored protein showed that it was identical to the DCCD reactive proteolipid or subunit c of mitochondrial adenosine triphosphate synthase and that it comprised approximately 50% of storage material. Based on the adage that the dominantly stored species should reflect the underlying biochemical anomaly, it was concluded that it was of pathogenic significance. This highly hydrophobic protein tends to extract with lipids in chloroform/methanol and is thus known as a proteolipid. Some of the remainder of the stored proteins also had this characteristic. It was concluded that ovine ceroid-lipofuscinosis was a proteinosis, more specifically a proteolipid proteinosis and as such it forms the prototype of a new class of storage diseases. Recognition of the nature of the dominantly stored chemical species has helped understanding of a variety of chemical and physical characteristics attributed to the whole pigment.(ABSTRACT TRUNCATED AT 250 WORDS)