This is an autosomal recessive trait that is caused by a defect in the enzyme homogentisic acid oxidase (EC 1.13.11.5). The enzyme normally breaks down a toxic tyrosine byproduct, homogentisic acid (also called alkapton), which is harmful to bones and cartilage and is excreted in urine.

Symptoms

A distinctive characteristic of alkaptonuria is that urine exposed to air turns dark (or black) after several hours because of the homogentisic acid. In adulthood, persons suffering from alkaptonuria develop progressive arthritis (especially of the spine), due to its degenerative effects on bones and cartilage.

Diagnosis

Presumptive diagnosis can be made by adding sodium or potassium hydroxide to urine and observing the formation of a dark brown to black pigment on the surface layer of urine within 30 minutes to 1 hour. Diagnosis can be confirmed by demonstrating the presence of homogentisic acid in the urine. This may be done by paper chromatography and thin-layer chromatography (Seegmiller, 1998).

Treatment

Prevention is not possible and the treatment is aimed at ameliorating symptoms.

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Spontaneous tendon ruptures in alkaptonuria/Author's reply
From Journal of Bone and Joint Surgery, 9/1/04 by Logani, V

Sir,

We read with interest the article by Manoj Kumar and Rajasekaran1 in the August 2003 issue entitled 'Spontaneous tendon ruptures in alkaptonuria'.

The authors have presented one of the rare manifestations of alkaptonuria and have stated that the numerous reports on alkaptonuria are limited to degenerative manifestations in joints, but there are no reports of the effects of deposition of homogentisic acid in tendons leading to spontaneous rupture. However, there are three articles in the literature that reported similar findings. Abe et al2 reported rupture of the tendo Achillis (TA) in a 59-year-old male among 13 cases of alkaptonuria from one family. The gross and histological findings of the frayed tendon ends were also similar to those reported by the current authors. Rupture of the TA in ochronosis has also been reported by DiFiore.' Borman, Bodur and Ciliz4 reported rupture of the anterior cruciate ligament in a 35-year-old alkaptonuric male. Furthermore, they have included tendinous calcification, ossification and rupture (frequently in the TA and menisci) among the diagnostic musculoskeletal features of ochronosis.

We would, therefore, like to highlight the fact that since deposition of polymers of homogentisic acid in tendons and ligaments is a part of the pathogenesis of ochronosis, spontaneous tendon ruptures in alkaptonuria should be considered a part of the natural history of the disease itself.

V. LOGANI, MS (Ortho)

K. K. EACHEMPATI, MS (Ortho)

R. MALHOTRA, MS (Ortho)

S. BHAN, MS (Ortho), FRCS

India Institute of Medical Sciences

New Delhi, India.

1. Manoj Kumar RV, Rajasekaran S. Spontaneous tendon ruptures in alkaptonuria. J Bone Joint Surg [Br] 2003:85-8:883-6.

2. Abe Y, Oshima N, Hatanaka R, Amako T, Hirohata R. Thirteen cases of alkaptonuria from one family tree with special reference to osteo-arthrosis alkaptonurica. J Bone Joint Surg [Am] 1960;42-A:817-31.

3. DiFiore JA. Ochronosis: report of a case. Arthritis Rheum 1960:3:359-63.

4. Borman P. Bodur H, Ciliz D. Ochronic arthropathy Rheumatol Int 2002:21:205-9.

Author's reply:

Sir,

We would like to thank Dr Malhotra and his team for their interest in our article. We agree that spontaneous tendon ruptures have heen previously cited as one of the manifestations of alkaptonuria in patients presenting with other musculoskeletal manifestations of the disease. The articles by Abe et al1 and Borman, Bodur and Ciliz~ that have been quoted, report tendon ruptures in patients presenting with the typical musculoskeletal manifestations of the disease. The single patient reported by Borman et al" had multiple peripheral joint pains and stiffness of the lower back for four years. This patient was found to have an anterior cruciate ligament insufficiently on examination which did not contribute significantly to his symptoms. The patient reported by Abe et al' sustained a rupture of the tendo Achillis while on his way to hospital for the treatment of lumbago due to ochronosis. It is noteworthy that this patient had low back pain for 25 years.

Our aim in presenting this report of three patients was to highlight the fact that spontaneous tendon ruptures could be the first manifestation of alkaptonuria in otherwise asymptomatic patients. All patients in our series were otherwise asymptomatic until the tendon rupture. In all of them, the suspicion of ochronosis was aroused only on the operating table by the finding of pigment deposition at the site of rupture. The clinical history of blackish discolouration of urine and a spine radiograph with typical findings were obtained after the surgery. Histological examination of the resected portions of the tendon showed deposition of pigment.

The standard orthopaedic textbooks3,4 do not mention an association between spontaneous tendon rupture and alkaptonuria.

S. RAJASEKARAN, MS, DNB, FRCS, MCh, PhD

Ganga Hospital

Coimbatore, India.

1. Abe Y, Oshima N. Hatanaka R, Amako T, Hirohata R. Thirteen cases of alkaptonuria from one family tree with special reference to osteoarthrosis alkaptonurica. J Bone Joint Surg [Ami 1960;42-A:817-31.

2. Borman P, Bodur H, Ciliz D. Ochronic arthropathy. Rheumatol lnt 2002.21:205-9.

3. Duthie RB. Arthritis and rheumatic diseases. In: Duthie RB. Bentley G, eds. Mercer's orthopaedic surgery. Ninth ed. London: Arnold, 1996.

4. Solomon L, Warwick D, Nayagam S. Apley's system of orthopaedics and fractures. Eighth ed. London: Arnold, 2001.

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