Alkaptonuria is a rare autosomal recessive disorder resulting from congenital deficiency of the enzyme homogentisic acid (HGA) oxidase. Due to lack of HGA oxidase enzymatic activity, HGA cannot be degraded and it accumulates in cartilage and connective tissues for years, then it forms blue-black pigmentation. Deposition of the pigment causes degenerative changes in cartilage, intervertebral disc and other tissues¹.

Although intervertebral disc degeneration is common in alkaptonuria, our review of the literature introduced only 13 patients, including ours, were treated surgically for lumbar disc herniation^2-10. Diagnosis of alkaptonuria after black colored lumbar discectomy material is a rare condition.

Here we present a case of alkaptonuria, in which the patient was diagnosed after lumbar discectomy.

A 27 year old man had a three year history of low back with left leg pain was admitted to our clinic. On his neurological examination, straight leg rising was positive at 15 degrees on the left, plantar flexion of left foot was moderately weak and there was hypoesthesia at S1 dermatome on the left side. Lumbosacral magnetic resonance imaging (MRI) revealed a large left sided prolapse of the intervertebral disc at the L5-S1 level (Figure 1).

Figure 1: MRI revealed a large left sided prolapse of the intervertebral disc at the L5-S1 level.

Patient was operated in prone position under general anesthesia. There were no change of color of skin, muscle and ligaments observed. Partial hemilaminectomy and foraminotomy was performed at L5-S1 level. Good decompression of the neural structures was achieved. During L5-S1 discectomy it was realized that the extruded disc material was found degenerated and black in color (Figure 2). The histological investigation of the disc material proved that the disc was degenerated and pigmented (Figure 3).

Figure 2: The discectomy material was black and degenerated.

Figure 3: The histological investigation showed that the disc was degenerated and pigmented with a characteristic ochre color.

Black disc material suspected as alkaptonuria. Physical re-examination revealed no discoloration of nasal and ear cartilages in our patient. Patient's urine turned black after standing several hours in air. Qualitative measurement of the HGA level in the urine (Benedict test) was also positive. These findings confirmed the diagnosis of alkaptonuria. The cardiology, rheumatology, dermatology, ophthal-mology and physical medicine and rehabilitation departments were consulted to determine the other areas of involvement. Neither other pathology nor involvement was determined at these consultations.

The patient's left leg pain disappeared completely. Phenylalanine and tyrosine-deficient diet, 100mg/day of vitamin C and 100mg/day of diclofenac sodium were started. He was discharged 1 week after surgery and placed under long-term follow-up.

Alkaptonuria is a rare autosomal recessive disorder with a low incidence of 0.001%¹. Ochronosis is the pigmentation of connective tissues in alkaptonuric patients. Clinical manifestations of ochronosis usually appear after the age of 30. These clinical manifestations consist of blue-black pigmentation of external ear and tympanic membrane, black discoloration of the cerumen, blue, black or brown staining of the sclera and blue to black tinting of the skin in the axillary and genital regions¹¹.

Due to HGA oxidase enzyme deficiency, HGA accumulates in connective tissue¹². The HGA accumulation in the tissue may cause a chemical irritation, which leads to degeneration and inflammation. It is likely that HGA attaches to connective tissue and affects the macromolecular structures and the interactions between them. Some suggest that HGA leads to degeneration of oxidant products. Benzochinon acetate that forms with HGA oxidation binds to collagen diagonal bonds and impairs the connective structure. On the other hand, oxidation causes free radical formation which affects the development of tissue damage and triggers the inflammation. Finally, clinical findings regarding damage in the connective tissue¹³.

Accumulation of HGA in the cartilage of joints and intervertebral discs causes degeneration of the cartilage and lead to intervertebral disc herniation mainly in the thoracic and the lomber area¹⁴. The disease generally begins with chronic backache and restriction in back movements. More rarely, it may begin with acute backache resulting from rupture of the annulus fibrosus¹. The first symptom was sciatica in approximately 17% of patients with alkaptonuria in one report¹⁵ and was back pain in 60% of patients in another¹⁶. In alkaptonuric spondylosis, degenerative changes may be seen along the whole of the spine; however the most common involvement is in the lumbar spine. The most common radiological changes of alkaptonuric spondylosis include squaring of vertebral bodies, intervertebral disc calcification, bridging syndesmophytes, and apophyseal joint involvement. When changes are advanced, the radiologic appearance is like bamboo spine¹⁷.

Although lumbar disc rupture is common in alkaptonuria, there were only 13 patients treated surgically (Table 1). Our review of the literature revealed that most of the cases were diagnosed as alkaptonuria after surgery, when blackened nucleus pulposus was noticed during surgery. All the surgically treated alkaptonuric patients showed significant improvement after lumbar discectomy as in our case.

Table 1: Surgically treated alkaptonuric patients with lumbar disc herniation.

Peripheral joint arthritis develops in the later stage and generally large joints are involved. Involvement of small joints is rare¹². Renal functions may be deteriorated in patients with alkaptonuria due to accumulation of pigment in prostate. Calcification in prostate gland may cause an obstruction and renal dysfunction due to obstruction may occur¹⁸. Cardiovascular involvement may also occur in alkaptonuric patients. Systolic murmurs were found 15-20% of the patients¹⁹. Aortic and mitral valve involvement is usually seen in alkaptonuria. Also atherosclerotic plaques may develop in these patients, in whom myocardial infarction is the most common cause of death²⁰.

There is no effective treatment of alkaptonuria. In medical treatment, phenylalanine and tyrosine deficient diet as well as high dose of ascorbic acid is suggested. Non-steroid anti-inflammatory drugs may be required for arthropathy. As a conventional treatment, physical therapy and rehabilitative interventions can cause notable symptomatic relief¹². In addition, the use of antioxidants such as n-acetyl cysteine and vitamin E has been showed to reduce HGA accumulation in vitro²¹.

Consequently, black disc material is a suspicious value for alkaptonuria in patients who undergo lumbar discectomy. These patients are candidates of other systemic involvements of alkaptonuria. After lumbar discectomy, where black disc material has been found, diagnosis of alkaptonuria is essential. These patients must be placed on long term follow-up.

Because only a few alkaptonuric patients treated surgically for lumbar disc disease have been reported, little is known about outcome. The review of the literature showed that all alkaptonuric patients, including ours, were significantly improved after lumbar discectomy. So, lumbar discectomy have been helpful in this patient group.