A 48-year-old man presented with progressively worsening bilateral knee pain and low backache for 6 years. The pain was mechanical in character, with no features suggestive of inflammatory arthritis. Baseline investigations, including ESR and CRP, were normal.

Nothing initially suggested a rare metabolic disorder until a simple question about his urine changed the direction of the evaluation. He reported a several-year history of darkening of the urine upon storage or standing. Examination revealed striking bluish-brown pigmentation of the sclera and grey-blue pigmentation along the palmar creases (Figure 1).

The radiographs added another piece to the puzzle. Bilateral knee radiographs demonstrated joint-space narrowing, subchondral sclerosis and dense calcification. The pelvic radiograph showed bilateral symmetrical hip joint-space narrowing with sclerosis, while the lumbar spine showed multilevel disc-space narrowing with prominent disc calcification and degenerative changes (Figure 2). Together, these findings were suggestive of ochronotic arthropathy.

Alkaptonuria is a rare autosomal recessive disorder caused by deficiency of homogentisate 1,2-dioxygenase, resulting in accumulation of homogentisic acid. Oxidation and polymerisation of homogentisic acid produces an ochre-coloured pigment that deposits in connective tissues, including cartilage, sclera, skin and tendons.¹ In this patient, qualitative testing for homogentisic acid in spot urine was positive, confirming alkaptonuria with ochronotic arthropathy.

What initially appeared to be ordinary degenerative joint disease was, in fact, the musculoskeletal manifestation of a rare metabolic disorder. The clues were hiding in plain sight, the darkening urine, pigmented sclerae, palmar pigmentation and characteristic radiographic changes.

 Figure 1 Clinical features of ochronosis in a patient with alkaptonuria.

1. Bluish-black pigmented deposits involving the sclera.

2. Bilateral palmar grey-blue pigmentation  

3. Urine sample showing the characteristic darkening from pale yellow when freshly voided (left) to dark brown after standing/alkalinisation (right). 

 Figure 2. Radiographic features of ochronosis.

(A) Bilateral knee osteoarthropathy with characteristic suprapatellar soft-tissue deposits; (B) Bilateral hip degenerative changes; (C,D) multilevel lumbar intervertebral disc-space narrowing with degenerative changes, consistent with ochronotic arthropathy.

 Reference:

1. Ranganath LR, Jarvis JC, Gallagher JA. Recent advances in the management of alkaptonuria. J Clin Pathol. 2013;66(5):367-373.