Description:

Alkaptonuria is a rare hereditary disease with a defective enzyme that results in increased homogentisic acid levels in the body. Homogentisic acid accumulates in multiple body parts and initializes tissue damage. Clinical manifestations such as pigmentation of the skin areas and joint destruction result in ochronosis. Nitisinone decreases serum and urinary homogentisic acid levels, improving morbidity by preventing and slowing the progression of alkaptonuria. Nitisinone-induced hypertyrosinemia causes keratopathy and mental ill effects, which can be managed by diet restriction and regular check-ups. A personalized approach is required for treatment by nitisinone. Low-dose oral nitisinone is associated with overall good results and a better safety profile. Alkaptonuria is caused by a deficiency of homogentisate 1, 2-dioxygenase (HGD), an enzyme that converts homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway [1]. In the absence of HGD, increased levels of HGA and its metabolites are excreted in the urine and accumulate in fibrous and cartilaginous tissues, such as bone, articular cartilage, and intervertebral disc [2]. At least 1000 individuals with alkaptonuria have been described in the literature, and the incidence of alkaptonuria is estimated to be between 1 in 250,000 to 1 in 1,000,000 live births [3]. The three major features of alkaptonuria are the presence of HGA in the urine, ochronosis (bluish-black pigmentation in connective tissue), and arthritis of the spine and large joints. Ochronosis arthropathy often requires knee, hip, or shoulder replacement, which usually provides pain relief and functional improvement [2]. Regarding the effects of alkaptonuria in the spine region, there are some case reports of sciatica and cervical or thoracic myelopathy [2,[4], [5], [6]]. However, to the best of our knowledge, lateral atlantoaxial joint arthritis in patients with alkaptonuria has not been reported. We herein report a case of a patient with alkaptonuria-associated lateral atlantoaxial joint arthritis treated successfully with occipital–cervical fixation.

Two cases of advanced alkaptonuria (AKU) with co-existing osteoporosis are described. Case 1 developed multiple non-vertebral fragility fractures, while Case 2 developed vertebral fragility fractures, both refractory to bisphosphonates. Difficulties in diagnosing osteoporosis in AKU complicated by extensive calcifying and ossifying spondylosis are discussed. Both patients continued to fracture despite nitisinone therapy for metabolic control of AKU, as well as bisphosphonate antiresorptive therapy for osteoporosis. Subsequently the patients were treated with teriparatide 20 μg subcutaneous injections daily for two years, leading to reduction in fractures soon after commencing therapy in both cases. Markers of bone remodelling P1NP and CTX were stimulated. No complications due hypercalcaemia or calcification were encountered in either case. We conclude that teriparatide is an effective adjunct in the treatment of AKU when bisphosphonates prove ineffective. Alkaptonuria, a rare disorder of homogentisic acid metabolism, can lead to aortic valvular calcification and stenosis.

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Maria
Journal Coordinator
Global Journal of Research and Review