Thoracic Myelopathy With Alkaptonuria

Akeda, Koji; Kasai, Yuichi; Kawakita, Eiji; Matsumura, Yoshihiro; Kono, Takako; Murata, Tetsuya; Uchida, Atsushi

doi:10.1097/brs.0b013e31816046ea

Cited by 25 publications

(7 citation statements)

References 17 publications

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“…Despite the high prevalence of intervertebral disc degeneration in AKU patients, neurologic symptoms caused by spinal diseases are rare. [ 11 ] Spinal compression, disc bulges, herniations as well as effacement of cerebrospinal fluid space abnormally affect the spinal signals resulting in multitude of symptoms ranging from numbness, tingling, and bladder problems to diffuse pain. Hence, numbness and tingling in lower extremities are indicative of advanced arthritic changes in spine.…”

Section: Discussionmentioning

confidence: 99%

Alkaptonuria, more than just a mere disease

Rana

Saeed

Abdullah

2015

Journal of Neurosciences in Rural Practice

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Alkaptonuria (AKU) is considered a rare autosomal recessive condition that results in an accumulation of homogentisic acid in body tissues and causes long-term clinical, neurological and psychological complications. We present a comprehensive evaluation of an atypical 46-year-old Caucasian male who developed all clinical diagnostic symptoms of AKU (ochronotic pigmentations, dark urine and clinical arthritis of major joints including spine) by 25 years of age, well before the typical age mentioned in many reviews. First signs of ochronotic ear pigmentations unexpectedly started appearing as early as 12 years of age. A long “disease-free” period typical in classical AKU patient was also absent. This case report highlights the importance of considering psychological issues in AKU patients. The patient showed symptoms of dysthymia reporting social isolation, diminished interest in pleasurable activities, feeling of worthlessness and irritability as major psychological issues. Early ochronotic pigmentation, advanced spinal myelopathy and arthropathy of major joints suggests aggressive course of the disease. Our patient underwent bilateral shoulder replacement due to AKU-induced arthropathy resulting in restoration of some range of motions. AKU is not fully understood and we recommend treating it as a multidimensional disease with simultaneous physiological, neurological and psychological effects. Early diagnosis, understanding of disease prognosis and emphasis on psychological health is needed to improve the quality of life of AKU patients.

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Section: Discussionmentioning

confidence: 99%

Alkaptonuria, more than just a mere disease

Rana

Saeed

Abdullah

2015

Journal of Neurosciences in Rural Practice

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“…Symptoms worsen from the fourth decade onwards, including renal stones, progressive kyphoscoliosis and impaired spinal and thoracic mobility 10. This causes poor pulmonary inflation/decreased respiratory reserve and disc disease/prolapsed, resulting in spinal stenosis, cord compression and myelopathy, as well as fractures of vertebrae and long bones 11 12. Development of painful spinal disease is inevitable over time.…”

Section: Clinical Featuresmentioning

confidence: 99%

Recent advances in management of alkaptonuria (invited review; best practice article)

2013

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Alkaptonuria (AKU) is an autosomal recessive condition arising as a result of a genetic deficiency of the enzyme homogentisate 1,2 dioxygenase and characterised by accumulation of homogentisic acid (HGA). Oxidative conversion of HGA leads to production of a melanin-like polymer in a process termed ochronosis. The binding of ochronotic pigment to the connective tissues of the body leads to multisystem disorder dominated by premature severe spondylo-arthropathy. Other systemic features include stones (renal, prostatic, salivary, gall bladder), renal damage/failure, osteopenia/fractures, ruptures of tendons/muscle/ligaments, respiratory compromise, hearing loss and aortic valve disease. Detection of these features requires systematic investigation. Treatment in AKU patients is palliative and unsatisfactory. Ascorbic acid, low protein diet and physiotherapy have been tried but do not alter the underlying metabolic defect. Regular surveillance to detect and treat complications early is important. Palliative pain management is a crucial issue in AKU. Timely spinal surgery and arthroplasty are the major treatment approaches at present. A potential disease modifying drug, nitisinone, inhibits 4-hydroxy-phenyl-pyruvate-dioxygenase and decreases formation of HGA and could prevent or slow the progression of disease in AKU. If nitisinone therapy is able to complement the biochemical 'cure' with improved outcomes, it will completely alter the way we approach the management of this disease. Greater efforts to improve recognition and registration of the disease will be worthwhile. Improved laboratory diagnostics to monitor the tyrosine metabolic pathway that includes plasma metabolites including tyrosine to monitor efficacy, toxicity and safety postnitisinone will also be required.

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“…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.…”

Section: Discussionmentioning

confidence: 94%