This article concerns the study of a family in which cases of ochronosis had been reported previously. In the present study thirteen members of the family were found to have alkaptonuria and six of these had bone and joint changes typical of ochronosis. The ages of the thirteen alkaptonurics studied here ranged from six to sixty-six years. One member, who had died at the age of forty-four, was not included in the study. The youngest patient showing changes in the bones and joints due to ochronosis was forty-three. The genealogy of this family showed a high incidence of consanguineous marriage.
In the twelve patients with alkaptonuria ochronosis was first observed in the auricles and then in the sclerae, finger nails, nose, and cheeks. Joint symptoms similar to osteo-arthritis appeared after pigmentation had developed, first as lumbago alone and then with the subsequent development of radiating pain in the lower extremities and pain in the joints, with limitation of motion.
Skeletal roentgenograms showed degenerative changes and the formation of spurs of the appendicular joints in five of the twelve patients studied. Joint changes first made their appearance in the lumbar spine, followed by changes in the thoracic and cervical regions. Changes in the other joints appeared subsequently.
In one patient (Case 2) histological examination of the Achilles tendon was possible when a ruptured tendon was repaired. The sections showed degeneration and necrosis of the tendon fibers and diffuse granular deposits of pigment, both within the cells of the tendon and within the extracellular spaces. While this patient was hospitalized he was maintained on a constant diet to which was added first DL-p-methoxyphenylalanine and then L-dihydroxyphenylalanine. No increase in the excretion of homogentisic acid in the urine resulted, and it was concluded that neither of these substances is a precursor of homogentisic acid.
An additional finding in this family was that among the members studied, those with alkaptonuria excreted more uric acid than the normal members of the family. It is suggested that the metabolism of uric acid and of the purine bases is disturbed in the alkaptonuric.