Ochronotic arthropathy as a paradigm of metabolically induced degenerative joint disease. A case-based review

Abstract

Alkaptonuria is a rare, hereditary metabolic disorder in which a deficiency in the homogentisate 1,2-dioxygenase enzyme results in an accumulation of homogentisic acid. Deposition of excess homogentisic acid in different intra- and extra-articular structures with high content of connective tissue causes brownish-black pigmentation and weakening, ultimately resulting in tissue degeneration and finally osteoarthritis. Ochronotic arthropathy is considered a rapidly progressive, disabling condition in which weight-bearing joints and the thoracolumbar spine are predominantly affected. Patients often require multiple joint replacements, such as in the case of the patient presented here. At present, there is no definitive cure for ochronosis, and management is predominantly symptomatic.

Septic arthritis in ochronosis’ patient

“…The classic clinical trial of alkaptonuria is homogentisic aciduria, ochronosis and ochronotic arthropathy. 7 Overall, the incidence of ochronotic arthropathy in patients with alkaptonuria is low. 2 Differential diagnosis must be done with ankylosing spondylitis and degenerative osteoarthosis.…”

“…2 Differential diagnosis must be done with ankylosing spondylitis and degenerative osteoarthosis. 7 However, certain radiologic findings allow its differentiation, like unusual sites of joint involvement (severe glenohumeral joint disease in the absence of significant trauma, advanced changes in the sacroiliac joints and symphyseal joints), and joint-space loss with an unusual pattern (symmetrical joint-space narrowing in the hips and shoulders, and isolated lateral femorotibial loss of knee joint space) ( Figure 4). Involvement of large peripheral joints usually occurs about 10 years after spinal changes.…”

“…Involvement of large peripheral joints usually occurs about 10 years after spinal changes. 7 Darkening of the urine is a common diagnostic feature and should be considered in children even producing it unusually. 2 Diagnosis can be confirmed using gas liquid chromatography, thin-layer chromatography, or enzymatic spectrophotometry to analyse the amount of homogentisic acid in the patient's urine.…”

“…2 Homogentisic acid and its oxidation products could accumulate also in the sclera, skin, heart valves, the cartilage of the nose and ears, tendons, ligaments, renal tubule epithelial cells, pancreas, and arteries. [5][6][7] In this paper, it is described a clinical presentation of ochronotic arthropathy with septic arthritis in the knee, of a complex patient.…”

Ochronotic Arthropathy

“…Spine radiographs showed severe disc space narrowing with calcification of the degenerated lower lumbar spine discs ( middle ), fusion of the upper lumbar spine disc spaces ( right ), and severe osteopenia; the sacroiliac joints were patent. Alkaptonuria is a rare autosomal‐recessive metabolic disorder in which a homogentisate 1,2‐dioxygenase enzyme deficiency leads to an accumulation of homogentisic acid (HGA) . The classic clinical triad of alkaptonuria is homogentisic aciduria, ochronosis, and ochronotic arthropathy.…”