Studies on the pathogenesis of ochronotic arthropathy

Abstract

TUDIES OF biochemical abnormalities in alcaptonuria during the course of S almost a century culminated recently in the demonstration that the basic defect is absence of homogentisic acid (HGA) oxidase in the tissues.l The mechanisms involved in the pathologic consequences of this biochemical defect have, however, been little studied or understood.The pathologic characteristics of the arthropathy that constitutes the principal lesion of ochronosis have been described in scattered instances.2 The anatomic findings in the knees in three cases that we have studied have suggested a number of mechanisms by which the alcaptonuric defect may cause pigmentation and damage to articular tissues. These observations as well as electronmicroscopic and certain in vitro studies of the reaction between articular cartilage and HGA provide the basis of the present report.CASE REPORTS Alcaptonuria in the three patients was proven by the reduction of Brigg's reagent by urine, and by enzymatic assay for HGA in both blood and urine.8 CASE 1. (No. 01-63-68). The patient was a 44 year old man dying of bronchogenic carcinoma. The clinical and hereditary aspects of this case have been reported previously.' At the age of 38 the patient began having severe pains in the low back, and two years later noted pain and grating sensations when moving the knees. Roentgenographic studies at this time revealed narrowing of the joint space between the patella and femur, osteophytes, and roughening of the articular surface of the patella. Radiopaque bodies were present in the suprapatellar and popliteal spaces.

Mutation Screening of theHGDGene Identifies a Novel Alkaptonuria Mutation with Significant Founder Effect and High Prevalence

“…Genetically, AKU is inherited as an AR trait (Virchow, 1866;Osler, 1904;Yules, 1957;O'Brien & Banfield, 1961). In our study, identical mutation in the homozygous state was identified in 11 of 16 nomads suffering from AKU.…”

Ochronosis masquerading as pigmented villonodular synovitis: a case report

“…The disease is not usually detected until adulthood because the only manifestation in childhood is darkening of urine. Arthritis tends to manifest in the third decade of life [1,5]. The most common serious effect of alkaptonuric ochronosis is the development of ochronotic arthropathy.…”

“…The patient generally presents in the 3rd decade of life with degenerative arthritis and the diagnosis is suspected based on pigmentation of the ear cartilage and urine turning black on standing [1][2][3][4][5][6][7][8][9]. Ochronosis masquerading as pigmented villonodular synovitis is extremely rare.…”

Total Knee and Hip Reconstruction in Male Patient with Alkaptonuria with 3 Years of follow up: Case Report and Review of the Literature

“…The most frequent manifestations of the disease are diffuse calcification of the intervertebral disk followed by narrowing of the intervertebral space and specific type of arthropathy of the axial skeleton and the peripheral joints. Peripheral arthritis is observed in almost all patients, as they grow in age [15,16]. It first appears in knees, hips, shoulders, seldom in small joints of hands, and it is manifested by pain, limited morbidity and hydrarthrosis.…”