Two previously undescribed disorders have been discovered in the Cayman Islands, British West Indies, in the course of a genetics survey conducted by the Principal Investigator: 1) a lethal Storage disease, suggestive of mucopolysaccharidosis or mucolipidosis; and 2) a disorder of cerebellar parenchymatous degeneration, designated Cayman disease. Both are inherited as autosomal recessives, with 7 living affecteds, 6 deceased presumed affecteds with Storage disease, and 27 affecteds with Cayman disease having been identified. We shall attempt to elucidate the specific molecular defect in each of these diseases, and to characterize them pathologically, genetically and biochemically. We propose to bring Storage disease and Cayman disease patients to the Columbia-Presbyterian Medical Center for intensive clinical evaluation. In addition, an in-depth analysis of lysosomal hydrolases in serum and cells of Storage disease affecteds and heterozygotes will be done, while the primary thrust of our Cayman disease research will be detailed biochemical studies of multiple tissues, cultured and uncultured, from the affected patients.