|Year : 2016 | Volume
| Issue : 1 | Page : 55-58
Prolapsed lumbar disc in alkaptonuria
Surapaneni Suresh Babu1, G Sudhakar2, PE Sonylal3, M.U.S.K. Sridevi4
1 Department of Orthopaedics, Dr. PSIMS & RF, Chinnoutpalli, Gannavaram, Andhra Pradesh, India
2 Department of Pathology, Government Medical College, Ananthapuram, Tamil Nadu, India
3 Department of Neurosurgery, Dr. PSIMS & RF, Chinnoutpalli, Gannavaram, Andhra Pradesh, India
4 Suresh Ortho Clinic, Vijayawada, Andhra Pradesh, India
|Date of Web Publication||18-Mar-2016|
Surapaneni Suresh Babu
Suresh Ortho Clinic, #56-2-20, Koneru Satyanarayana Street, Patamata, Vijayawada - 520 010, Krishna Dt., Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Alkaptonuria (AKU) is a rare autosomal recessive disorder caused by deficiency of homogentisate 1,2-dioxygenase, an enzyme that converts homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway. The three major features of AKU are the presence of HGA in the urine, ochronosis (bluish-black pigmentation in connective tissue), and arthritis of the spine and larger joints. We present a case of 48-year-old woman with a history of low back pain and left sided sciatica. Preoperative radiograph and computed tomography scan showed multiple calcified discs. Magnetic resonance imaging demonstrated an extruded disc at L4-L5, which was the culprit for her symptoms. She underwent complete discectomy. During discectomy, the disc found to be brittle and dark pigmented. Histopathology reported the disc had ochronoid pigment, and her urine turns dark after alkalization, and she admitted that she passed dark urine since childhood. Prolapsed lumbar disc is a rare entity in calcified discs of ochronotic spine. It requires discectomy in symptomatic patients. It requires long-term follow-up.
Keywords: Alkaptonuria, inter vertebral disc prolapse, ochronosis spine
|How to cite this article:|
Babu SS, Sudhakar G, Sonylal P E, Sridevi M. Prolapsed lumbar disc in alkaptonuria
. J NTR Univ Health Sci 2016;5:55-8
| Introduction|| |
First described in1866 alkaptonuria (AKU) is a rare autosomal recessive disorder caused by deficiency of homogentisate 1,2-dioxygenase, an enzyme that converts homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway. The three major features of AKU are the presence of HGA in the urine, ochronosis (bluish-black pigmentation in connective tissue), and arthritis of the spine and larger joints. Oxidation of the HGA excreted in the urine produces a melanin-like product and causes the urine to turn dark upon standing. Ochronosis occurs only after age 30 years, arthritis often begins in the third decade. Other manifestations include pigment deposition, aortic or mitral valve calcification or regurgitation and occasionally aortic dilatation, renal stones and prostate stones.
The diagnosis of AKU is based on the detection of a significant amount of HGA in the urine by gas chromatography-mass spectrometry analysis. The amount of homogentisic acid (HGA) excreted per day in individuals with AKU is, usually, between 1 and 8 g. HGD, the gene encoding homogentisate 1,2-dioxygenase, is the only gene in which mutations are known to cause AKU. Management of joint pain tailored to the individual; physical and occupational therapy to help maintain muscle strength and flexibility; knee, hip, and shoulder replacements when needed; surgical intervention for prostate stones and renal stones as needed; aortic stenosis may necessitate valve replacement.  Here, we present a case who presented to us as posterior intervertebral disc prolapse, with symptomatic sciatica in her fourth decade even she passes dark urine since childhood.
| Case report|| |
A 48 years woman was seen by us and multiple consultants for persistent low back pain and left sided sciatica. She was treated conservatively. Her symptoms were not relieved, and she was worked up by radiograph, computed tomography (CT) scan and magnetic resonance imaging (MRI) scan. Radiograph showed calcification of the spine and intervertebral discs calcification, which were unusual for her age and occupation [Figure 1]. CT also showed disc calcification [Figure 2], MRI showed significant protruded disc prolapse at L4-L5 along with other degenerated discs [Figure 3]. Clinically we confirmed that the extruded disc at L4-L5 was the reason for her symptoms, she underwent L4 laminectomy and L4-L5 discectomy. During the surgery, we found the disc was fragile and black pigmented [Figure 4]. Keeping ochronosis in mind we questioned the patient, and she admitted that her urine would become dark colored on prolonged standing since her childhood. The histopathology of the disc showed ochronoid dark stained pigment depositions in H and E staining [Figure 5]a. Her urine demonstrated dark change on adding an alkali [Figure 5]b. Chemical test of the urine confirmed the presence of HGA.
|Figure 1: Radiograph showing multiple calcified discs along with diffused arthritic changes in spine|
Click here to view
|Figure 3: Magnetic resonance imaging scan showing L4-L5 extruded disc with left sided foramen compression|
Click here to view
|Figure 5: (a) HPE-revealed a granular blackish brown pigment of inter vertebral articular cartilage and collagen fibers (b) Development of black color after alkalinization of urine|
Click here to view
Her symptoms were totally relieved, and she was followed for 2 years. She was informed about the disease and its prognosis and a further chance of involving skin, eyes, ears, cardiovascular system and renal stones.
| Discussion|| |
Even though, spine involvement in ochronosis is common, ochronosis shows a very low prevalence (1:100,000-250,000) in most ethnic groups. One notable exception is in Slovakia, where the incidence of AKU rises to 1:19,000. Only a few cases have been reported from India. Most of them are from Tamil Nadu, Karnataka and Andhra Pradesh, prevalence and incidence are variable from country to country. ,,,,, Patients with mild AKU may remain asymptomatic, the condition remaining unrecognized throughout the life. On the contrary, severe effects may manifest quite early, by observing that the infant's nappies become darkly stained on washing with an alkaline soap or on exposure to air. , However, more commonly the cases are recognized in the fourth or fifth decades with a peak incidence in the fifth decade.  Our patient had become symptomatic in the fourth decade of her life even though she used to pass dark urine since childhood that is unusual. Most of the cases are recognized in adult life, by observing the staining of clothes at the axilla and by the development of pigmentation in the pinnae, sclera or the skin. 
Ochronotic arthropathy, usually, presents late in adult life, with symptoms worsening with progression of age. However, in severe cases arthropathy may occur much earlier.  Spine is, usually, the first area to be affected, with patients complaining of stiffness and low back pain. Localized kyphosis or scoliosis may occur. Lordosis of the lumbar and cervical spine is flattened.  Occasionally, patients present with sciatica, thoracic compressive myelopathy with a complaint of a root pain. ,, In our case she presented with low back pain along with left sided sciatica. In AKU, deposition of a polymer of HGA and its oxidation products (e.g., benzoquinone acetic acid), a dark yellow pigment or "Ochre" occurs in the cartilage and other connective tissues. 
This deposition causes the disc to lose its fluidity and makes disc brittle and fragmented.  But In our case it was presented as prolapsed intervertebral disc, which was unusual even though disc lost its hydration and became fragile. Disc ruptures are much more frequent in males than females that were dissimilar to our case. 
Radiologic changes sometimes precede the onset of patient's symptoms. In the spine, the changes commence in the thoraco-iumbar region. Due to pigment deposition and subsequent calcification, the vertebral surfaces of the discs become increasingly radio dense, which is seen as "doubling" of the outlines.  The condition continues to progress with an increase in the radiodensity of the discs. Intradiscal lucencies secondary to vacuum phenomenon may occur. The nucleus pulposus is the last part of the disc to become calcified.
Vertebral osteoporosis occurs, which may lead to kyphoscoliotic deformities secondary to compression fractures.  Massive osteophyte formation, sub-chondral sclerosis, cyst formation and ultimately bony ankylosis may occur.  In knee joints, early change occurs in the form of meniscal calcification. Subchondral increased density occurs with scattered osteoporotic areas in the tibia and femoral condyles. Asymmetric joint space narrowing and marginal osteophytosis develop. Calcified loose bodies, subchondral cysts and sclerotic islands representing avascular necrosis may occur.  Similar changes may develop in shoulders and hips, with flattening of the femoral and humeral heads. 
Although ankylosing spondyl itis, rheumatoid arthritis and age-related degenerative spondylitis have been included in the differential diagnosis of ochronotic spine, the roentgen changes seen in most of the cases are pathognomonic of the diagnosis and simple urine examination in these cases will confirm the diagnosis.
Urine of such patients turns dark on standing or when alkalinized, owing to the oxidation of HGA.  In our case also the classical presentation mentioned above was seen in both CT and radiograph, and urine became dark after adding an alkali.
Corrective surgical procedures such as disc removal or decompression of the spinal cord have been a success in selected patients. ,, Very few cases were recorded in literature that underwent decompressive surgery, ours is one such case we presented. Postoperatively the patient had excruciating pain on other side, that is, right sided sciatica probably due to irritation of HGA products which was subsided by high dose of steroids.
In conclusion, prolapsed lumbar disc is a rare entity in calcified discs of ochronotic spine. It requires discectomy in symptomatic patients. It requires long term follow-up.
| References|| |
Introne WJ, Gahl WA. Alcaptonuria. Gene Rev 2013;???:???.
Laskar FH, Sargison KD. Ochronotic arthropathy. A review with four case reports. J Bone Joint Surg 1970;52B:653-64.
Zatková A, de Bernabé DB, Poláková H, Zvarík M, Feráková E, Bosák V, et al.
High frequency of alkaptonuria in Slovakia: Evidence for the appearance of multiple mutations in HGO involving different mutational hot spots. Am J Hum Genet 2000;67:1333-9.
Tharini G, Ravindran V, Hema N, Prabhavathy D, Parveen B. Alkaptonuria. Indian J Dermatol 2011;56:194-6.
Das KM, Chakraborty K, Pandey SK, Middya AK, Mandal PK, Ballav A. Rehabilitation of a Patient with alkaptonuric (ochronotic) arthritis. IJPMR 2007;18:54-7.
Cervenansky J, Sitaj S, Urbanek T. Alkaptonuria and ochronosis. J Bone Joint Surg Am 1959;41-A:1169-82.
O′Brien WM, La Du B, Burin JJ. Ochronotic arthropathy. Am J Med 1963;34:813-7.
Gupta RP, Mohan V, Hantlra II, Bang RL. Ochronotic arthropathy. J Kuwait Med Assoc 1987;21:339-41.
Lagier R, Sit′aj S. Vertebral changes in ochronosis. Ann Rheum Dis 1974;33:86-92.
Akeda K, Kasai Y, Kawakita E. Thoracic Myelopathy with alkaptonuria. Spine 2008;33:E62-5.
Lumbar spine herniation with neurological symptoms in a young patient with ochronosis and alkaptonuria. A case report. Posted by BODY HOLISTICA on Sunday, January 17, 2010.
Detenbeck LC, Young HH, Underdahl LO. Ochronotic arthropathy. Arch Surg 1970;100:215-9.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]