MUSCLE MORPHOLOGY AND MITOCHONDRIAL INVESTIGATIONS OF A FAMILY WITH AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA AND RETINAL DEGENERATION MAPPED TOCHROMOSOME 3P12-P21.1

The autosomal dominant cerebellar ataxias (ADCA) are a group of neurod egenerative disorders with ataxia and dysarthria as early and dominant signs. In ADCA type II, retinal degeneration causes severe visual imp airment. ADCA type II has recently been mapped to chromosome 3p by thr ee independent groups. In the family with ADCA type II studied here, t he disease has been mapped to chromosome 3p12-p21.1. Histochemical exa mination of muscle biopsies in 5 cases showed slight neurogenic atroph y and irregular lobulated appearance or focal decreases of enzyme acti vity when staining for NADH dehydrogenase, succinic dehydrogenase and cytochrome oxidase. Ragged-red fibres were scarce. Electron microscopi c examination showed uneven distribution of mitochondria with large fi bre areas devoid of mitochondria and/or large subsarcolemmal accumulat ions of small rounded mitochondria. and frequent autophagic vacuoles. These vacuoles contained remnants of multiple small rounded organelles , possibly mitochondria, and had a remarkably consistent ultrastructur al appearance. Biochemical investigation of mitochondrial function sho wed reduced activity of complex IV and slightly reduced activity of co mplex I in the respiratory chain in a severely affected child while no abnormalities were found in his affected uncle.