Alkaptonuria is the result of loss of function, missense mutations of the gene on chromosome 3q that codes for homogentisate 1, 2 dioxygenase (HGA). Scribonius first described the urinary manifestations of the disease in 1584, and Boedeker in 1858 recognized the presence in urine of a reducing substance (alkapton) with an affinity for oxygen in an alkaline medium. Virchow noted the ochre (yellow)-coloured pigmentation in histological sections of postmortem tissues that lead to the term "ochronosis" [2
The pathogenesis of the spinal manifestations in the lumbar region can be explained as follows. Raised blood levels of homogentisic acid lead to deposition of pigmented benzoquinone polymeric oxidation products of homogentisic in chondrocytes, type 2 collagen fibres of the ligaments and elastic cartilages [3
]. The axial loading of the body weight is maximum at the lower lumbar spine, because of which it undergoes early and accelerated age related degenerative changes. This disrupts the integrity of the spinal stabilizing systems - passive (disc, ligament, bone, and passive muscle), active (tendons and active muscle) and neural (the nervous system and neural components within the passive and active structures), causing a transfer in unfavorable loads onto other spinal structures [4
]. The presence of a calcified disc and stiff spine anteriorly causes transfer of mechanical forces to the posterior ligamentous structures of the spine, resulting in increased expression of tissue inhibitors of matrix metallaprotinase-2 in ligamentum flavum fibroblasts with resultant fibrosis and hypertrophy of the ligamentum flavum [5
]. The ochronotic deposits accelerate further calcium deposition in the ligaments enhancing their stiffness. Vacuum disc phenomenon presumably represents areas of severe degeneration within the intervertebral disc [6
]. Our patient had calcificied intervertebral discs at L2/3 and L3/4 which would have resulted in transfer of axial load at these immobile levels to the posterior elements at L4/5 level, which is the mobile segment in the immediate vicinity below.
A preoperative computed tomographic (CT) examination helps in identifying calcified disc protrusion (elliptical wafer appearance), ossified ligamentum flavum, osteophytes or degenerated facets which would necessitate the use of a high speed drill intraoperatively to remove the compressing element. The striking feature on MRI is multiple level disc prolapse, most common in the lumbar spine, with uniformly prominent low signal on T2WI in all discs suggesting disc degeneration and "Universal Calcification". The other findings include Schmorl nodules in the cartilage endplates, bone cysts [7,8
Irrespective of the pathogenesis, surgical decompression of the offending element causing spinal stenosis (protruded disc or hypertrophied ligamentum flavum) remains the treatment modality. Protein restriction and treatment with ascorbic acid may reduce plasma HGA levels, but treatment with nitisinone, which blocks HGA production and reduces HGA levels, is currently considered to be the best hope for treatment of these patients.
Disc prolapse in lumbar and dorsal spine of ochronotic patients has been reported previously [1,8-10
]. In all the case reports of lumbar and dorsal disc prolapse in ochronotic patients published in literature, there is no mention of ligamentum flavum hypertrophy associated with ochronotic deposits. Hence, this unusual spinal manifestation of hypertrophied ligamentum flavum with ochronotic depostis should be considered in the differential diagnosis of alkaptonuria patients presenting with neurogenic claudication. Such patients should be evaluated with both MRI and CT scan of the involved segment for reasons discussed earlier.