Late Infantile Neuronal Ceroid Lipofuscinosis : Abnormalities in the Polyunsaturated Fatty Acid Profiles of Phospholipids in Cultured Skin Fibroblasts

Abstract

Neuronal ceroid lipofuscinosis (NCL) is a group of inherited syndromes (Zeman et al., 1970), characterized by the accumulation of autofluorescent lipopigments (ceroid) similar to lipofuscin (age pigments) in neurons and other cells of patients (Hooghwinkel et al., 1986). The pigment deposition can proceed more or less rapidly and electron microscopic studies (Haltia et al., 1973 ; Arsenio-Nunes and Goutieres, 1975 ; Curless et al., 1982) revealed the three conventional cytosome types with a predominance of granular inclusions in the early infantile form, also known as “Polyunsaturated Fatty Acid Lipidosis” (PFAL) (Santavuori et al., 1973 ; Svennerholm et al., 1975 ; Bourre et al., 1979 ; Svennerholm et al., 1987). Curvilinear bodies are seen in the late infantile form, and fingerprint bodies are present in the juvenile form. A great variety of intra cytoplasmic inclusions were demonstrated in adult NCL and in atypical cases (Dom et al., 1979 ; Arsenio-Nunes et al., 1981 ; Rumbach et al., 1983). The most common genetic defect in the disease concerns an autosomal recessive trait. However, families with an autosomal dominant transmission were also described (Brodner et al., 1976 ; Badurska et al., 1981). The presence of lipofuscin-like material oriented the studies toward fatty acid metabolism, and lipid peroxide formation, implicating oxygen toxicity (Dillard and Tappel, 1971 ; Pullarkat et al., 1978). High levels of long chain polyisoprenoid alcohols of the dolichol class were recently demonstrated in human NCL brain and urinary sediment (Ng Ying Kin et al., 1983 ; Wolfe et al., 1983).