SCA34 caused by ELOVL4 L168F mutation is a lysosomal lipid storage disease sharing pathology features with neuronal ceroid lipofuscinosis and peroxisomal disorders

AbstractSpinocerebellar ataxia 34 (SCA34) is a late-onset progressive ataxia caused by a mutation inELOVL4, a gene involved in the biosynthesis of very long-chain fatty acids (VLCFAs). We performed post-mortem neuropathological examinations on four SCA34 patients with theELOVL4 L168F mutation and compared the findings to age-matched controls. Specific gross findings of SCA34 were limited to pontocerebellar atrophy. On light microscopy, pontine base showed neuronal loss and storage of an autofluorescent lipopigment positive on oil red O, PAS and Hale ’s colloidal iron and negative on Alcian blue and Luxol fast blue (LFB). Among the swollen neurons were abundant CD68+ /CD163+ /IBA1- macrophages laden with a material with similar histochemical profile as in neurons except for the lack of autofluorescence and oil red O positivity and the pres ence of needle-like birefringent inclusions. Normal resting IBA1 + microglia were generally absent from pontine base nuclei but present in normal numbers elsewhere in the pons. In dentate nucleus neurons, atrophy was milder than in the pontine base and the coarser storage material was LFB-positi ve, closely resembling lipofuscin. On electron microscopy, dentate nucleus neurons showed neuronal storage of tridimensionally organized trilaminar spicules within otherwise normal lipofuscin, while in the more affected pontine base neurons, lipofuscin was almost completely replaced by the storage m aterial. Storage macrophages were tightly...
Source: Acta Neuropathologica - Category: Neurology Source Type: research