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 regions
11.
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.
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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.
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