Biochemical, pathologic and clinical aspects of alcaptonuria, ochronosis and ochronotic arthropathy: Review of world literature (1584–1962)

Abstract

The biomedical literature on alcaptonuria, ochronosis and ochronotic joint disease, including 604 cases reported from thirty-five countries, is reviewed. The history of the development of our knowledge concerning this hereditary metabolic disorder, from 1584 to 1962, is recapitulated. The nature of the biochemical defect, a deficiency of homogentisic acid oxidase, in alcaptonuria is described and the pattern of genetic transmission traced. The geographic and racial distribution, and the multisystemic clinical manifestations of ochronosis are summarized. The diagnostic features and differential diagnostic considerations are presented. The gross, histopathologic and electron microscopic changes as well as pathogenesis are discussed. The various types of treatment attempted, without success, are mentioned.