Direct repair of the chronic ochronotic Achilles tendon rupture: a case report.

BACKGROUND: Alkaptonuria (AKU) is a rare hereditary disease. Ochronotic arthropathy, tendinopathy, and osteopenia/osteoporosis are generally musculoskeletal manifestations in patients with AKU. Because of the ochronotic tendinopathy and osteopenia, the surgical strategy for chronic ochronotic Achilles tendon rupture may be challenging. No studies have reported the surgical treatment of chronic Achilles tendon rupture in patients with AKU. CASE PRESENTATION: We report a case of AKU that required surgical treatment for chronic Achilles tendon rupture. A 60-year-old woman was referred to our department for the assessment of left hindfoot pain that persisted for more than nine months after an ankle sprain. Three years prior to the first presentation to our hospital, she was diagnosed with AKU due to pigmented hip cartilage at the time of total hip arthroplasty. The patient was diagnosed as chronic Achilles tendon rupture based on the results of physical examination and magnetic resonance imaging (MRI). The MRI showed enlarged scar tissue of the Achilles tendon with an intrasubstance high signal intensity. We performed resection of the central part of the scar tissue (total length, 24 mm) followed by direct repair using the proximal and distal stumps of the scar tissue. The MRI at 12months after surgery showed continuity of the repaired Achilles tendon. At 18 months after surgery, the Achilles Tendon Total Rupture Score improved from 22 points preoperatively to 84 points postoperatively. The foot and ankle outcome score also improved. CONCLUSIONS: We reported a case of AKU with chronic Achilles tendon rupture in which direct repair using scar tissue between the tendon stumps was effective. Careful selection of the surgical procedure for the treatment of chronic ochronotic Achilles tendon rupture is recommended because of concomitant ochronotic tendinopathy and osteopenia/osteoporosis.

Alkaptonuric Ochronosis: A case-based review.

Alkaptonuria (AKU) is an extremely rare autosomal recessive metabolic disorder caused by deficiency of homogentisic acid oxidase and resulting in accumulation of homogentisic acid in collagenous structures. It is characterized by a triad of homogentisic aciduria, bluish-black discoloration of connective tissues (ochronosis) and arthropathy of large weight bearing joints. We report on a middle-aged female patient with bilateral severe ochronotic arthritis of both hips and shoulder joints requiring total joint replacements as staged procedures which were done without complications offering a complete pain relief and a satisfactory clinical and functional outcome. Ochronosis can cause severe arthropathy of peripheral joints. Multiple joint affection is common. Total joint replacement can yield persistent pain relief with complete functional recovery in patients with severe ochronotic arthropathy.

Ease of sutureless aortic valve replacement in a patient with unexpected ochronosis: a case report.

BACKGROUND: Alkaptonuria is a rare congenital metabolic disorder characterized by homogentisic acid accumulation in body cartilage and connective tissues due to a deficient homogentisic acid dioxygenase enzyme. This disorder manifests in various clinical symptoms, including spondyloarthropathy, ocular and dermal pigmentation, genitourinary tract obstruction by ochronosis stones, and cardiovascular system involvement. Cardiac ochronosis is a rare manifestation of alkaptonuria that may present as aortic stenosis, sometimes accompanied by other cardiovascular complications. CASE PRESENTATION: We report an unexpected case of ochronosis diagnosed during cardiac surgery. Due to the fragile, thin, and atheromatous nature of the ascending aorta in patients with ochronosis, we opted for a sutureless aortic valve replacement procedure. This approach appears to be more suitable for patients with ochronosis. CONCLUSIONS: Although cardiac ochronosis is rare, surgeons should remain vigilant and consider the possibility of this condition when examining patients with aortic valve stenosis, paying close attention to the clinical manifestations of alkaptonuria.

Pseudofilariasis, a Presenting Sign of Alkaptonuria.

PURPOSE: To report the association of Pseudofilariasis as a presenting sign of Alkaptonuria. METHOD: Case Report. RESULTS: A 49-year-old Indian man was referred because of wormlike objects in his left conjunctiva. Ocular and family history was non-contributory. He had not been to India in 15 years. Past medical history revealed hypertension, hypercholesterolemia, arthritis, and a myocardial infarct. He had undergone two stents, bilateral Achilles tendon repairs and bilateral knee replacements. ROS showed longstanding back stiffness and pain. On ocular examination the vision was 20/25 in each eye and positive findings were in the left eye bulbar conjunctival which showed stationary black vermiform (filarial in appearance) foreign bodies along with 2 small corneal limbal pigmented deposits. Conjunctival biopsy showed dilated lymph channels with interstitial proteinaceous material of a light brown color consistent with Ochronotic pigment; hence diagnostic of Alkaptonuria. CONCLUSIONS: Pseudofilariasis may be a presenting sign of Alkaptonuria and occur years before a clinical diagnosis is made. Filariasis is always involves white worms and never black. Knowing the ophthalmic signs of this rare disease may lead to an accurate diagnosis earlier thusly avoiding unnecessary tests and examinations.

Disc-coloration of an ochronotic cervical intervertebral disc in a patient with alkaptonuria: Case report and review of the literature.

OBJECTIVES: Alkaptonuria is a rare inborn disorder of phenylalanine and tyrosine metabolism. It is characterized by an accumulation of homogentisic acid and its oxidation products, possibly resulting into connective tissue damaging. "Ochronosis" is a main feature, which is characterized by tissue discoloration and even alkaptonuric arthropathy. Cervical spine involvement is exceptional and there is a paucity of reports on surgical interventions in these patients. We explored the literature concerning cervical spine involvement in patients with alkaptonuria. PATIENTS AND METHODS: We performed a review of the literature, in which patients with alkaptonuric degenerative changes of the cervical spine were examined. Articles were obtained from MEDLINE. Search terms included: "cervical", "alkaptonuria", "alkaptonuric changes" and "black disc". Additional studies were identified by checking reference lists. Furthermore, we present the case of a 46 year old patient with critical cervical spinal canal stenosis who underwent C6-C7 anterior cervical microdiscectomy and interbody fusion, in order to prevent myelopathic changes. CARE statement guidelines were followed. RESULTS: Peroperatively, we did not encounter any macroscopic abnormalities of the skin, muscles or ligaments. A black discoloration of the nucleus pulposus was observed. Peroperative and postoperative course was uneventful. CONCLUSION: Alkaptonuric degenerative abnormalities most commonly involve the lumbar spine, although the cervical spine can be affected in rare cases. Most frequently, the diagnosis of alkaptonuria can be made based on the clinical phenotype many years before symptoms secondary to ochronotic arthropathy develop. A retrospective diagnosis based on peroperative black discoloration of spinal structures has been described. A black discoloration of the intervertebral disc should encourage the neurosurgeon to further explore the possibility of alkaptonuria, even in the absence of a clear phenotype. Surgical results are mostly satisfactory. Further studies are required in order to better understand this pathology and its postoperative course.

Alkaptonuria.

Alkaptonuria is a rare inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase activity. The consequent homogentisic acid (HGA) accumulation in body fluids and tissues leads to a multisystemic and highly debilitating disease whose main features are dark urine, ochronosis (HGA-derived pigment in collagen-rich connective tissues), and a painful and severe form of osteoarthropathy. Other clinical manifestations are extremely variable and include kidney and prostate stones, aortic stenosis, bone fractures, and tendon, ligament and/or muscle ruptures. As an autosomal recessive disorder, alkaptonuria affects men and women equally. Debilitating symptoms appear around the third decade of life, but a proper and timely diagnosis is often delayed due to their non-specific nature and a lack of knowledge among physicians. In later stages, patients' quality of life might be seriously compromised and further complicated by comorbidities. Thus, appropriate management of alkaptonuria requires a multidisciplinary approach, and periodic clinical evaluation is advised to monitor disease progression, complications and/or comorbidities, and to enable prompt intervention. Treatment options are patient-tailored and include a combination of medications, physical therapy and surgery. Current basic and clinical research focuses on improving patient management and developing innovative therapies and implementing precision medicine strategies.

Arthroscopic ankle arthrodesis in two alkaptonuria patients.

Alkaptonuria is a very rare disorder in which homogentisic acid accumulates due to a deficiency in the activity of homogentisic acid 1,2 dioxygenase. This deficiency results in deposition of a yellowish-brown pigment in connective tissue. Such deposition is termed 'ochronosis' and leads to deterioration in the formation and structure of proteoglycans in hyaline cartilage. These actions lead to fragmentation and rapid destructive arthritis. Often, ochronotic arthritis appears at 40-60 years of age, and many patients are treated symptomatically. Here, we report two patients (three ankles) with ochronotic arthritis who were treated with ankle arthrodesis. In all cases, the postoperative clinical score improved, but the time needed for fusion was prolonged and symptomatic subtalar arthropathy developed in the early postoperative period.

Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies.

Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA > 10 mg/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA > 10 mg/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis.

Minocycline induced discoloration of the aortic intima and valve: A case report.

CASE REPORT: Ochronosis refers to the blue-black discoloration of connective tissue. While cardiovascular ochronosis has been described resulting from alkaptonuria, it may also result from chronic minocycline use which is exceedingly rare. Cardiovascular ochronosis often presents with insidious development, often identified incidentally during aortic valve replacement (AVR). Herein, we describe the case of a 71-year-old male undergoing AVR and coronary artery bypass grafting found to have minocycline-induced ochronosis of the aortic valve and aorta. CONCLUSIONS: Given the rarity of this case, descriptions of cardiovascular ochronosis cases secondary to minocycline use are imperative in ensuring that it is on the differential diagnosis when identified by others in future cases. Additional care must be taken intraoperatively to ensure that the correct anatomy is identified as discoloration hinders visualization of the anatomy potentially resulting in unintentional consequences such as heart block or perivalvular leak as traditional visual cues for suture placement are distorted.

Radiological evolution of spinal disease in alkaptonuria and the effect of nitisinone.

OBJECTIVES: Ochronotic spondyloarthropathy represents one of the main clinical manifestations of alkaptonuria (AKU); however, prospective data and description of the effect of nitisinone treatment are lacking. METHODS: Patients with AKU aged 25 years or older were randomly assigned to receive either oral nitisinone 10 mg/day (N=69) or no treatment (N=69). Spine radiographs were recorded yearly at baseline, 12, 24, 36 and 48 months, and the images were scored for the presence of intervertebral space narrowing, soft tissue calcifications, vacuum phenomena, osteophytes/hyperostosis and spinal fusion in the cervical, thoracic and lumbosacral segment at each of the time points. RESULTS: At baseline, narrowing of the intervertebral spaces, the presence of osteophytes/hyperostosis and calcifications were the three most frequent radiographic features in AKU. The rate of progression of the five main features during the 4 years, ranked from the highest to lowest was as follows: intervertebral spaces narrowing, calcifications, vacuum phenomena, osteophytes/hyperostosis and fusions. The rate of progression did not differ between the treated and untreated groups in any of the five radiographic parameters except for a slower rate of progression (sum of all five features) in the treatment group compared with the control group (0.45 (1.11) nitisinone vs 0.74 (1.11) controls, p=0.049) in the thoracic segment. CONCLUSION: The present study shows a relatively slow but significant worsening of radiographic features in patients with AKU over 4 years. Our results demonstrate a modest beneficial effect of 10 mg/day of nitisinone on the slowly progressing spondylosis in AKU during the relatively limited follow-up time. TRIAL REGISTRATION NUMBER: NCT01916382.

Ochronotic arthropathy in the context of spondyloarthritis differential diagnosis: a case-based review.

Alkaptonuria is a disease often forgotten because of its rarity. Its pathogenic mechanism is the deficiency of one of the enzymes of the tyrosine degradation pathway-homogentisate-1, 2-dioxygenase, which sequelae is accumulation and deposition of its metabolite homogentisic acid in connective tissues and urine. Alkaptonuria presents as a clinical triad-darkening urine upon prolonged exposure to air, pigmentation of connective tissues and debilitating arthropathy. We present a case report of a 67-year old patient with alkaptonuria who presented with the clinical triad, but was mistakenly diagnosed as having ankylosing spondylitis in the past. Currently there is no treatment for the disease hence the management strategy was focused on symptoms control with analgesics, physical therapy, dietary modification, vitamin C supplementation, and joint arthroplasty. Alkaptonuria's clinical features are extensively described in the literature and despite the fact that it is a rare disease, due to the similar radiographic changes with spondyloarthropathies, it should be included in the differential diagnosis in young patients presenting with severe joint involvement. Early recognition of the disease is necessary since its natural evolution is joint destruction leading to significant reduction in the quality of life. Alkaptonuria's articular features in the spine and peripheral tissues are well described using the classical imaging techniques. Musculoskeletal ultrasonography shows a characteristic set of findings in the soft tissues, including synovium, cartilage, tendons and entheses.

Total Knee Replacement in Alkaptonuric Ochronosis.

BACKGROUND AND OBJECTIVE: Alkaptonuria is a rare disease characterized by the accumulation of homogentisic acid (HGA). Over time, these patients may develop disabling ochronotic arthropathy. We present 2 cases of patients with end-stage arthropathy treated with total knee arthroplasty (TKA). METHODS: Both patients complained of disabling knee pain and reported limited walking distance (200-300 m). One had a history of osteotomy for medial knee arthtritis and ignored his underlying condition. The other presented with valgus gonoarthrosis and diagnosis of alkaptonuria. RESULTS: Intraoperatively, the characteristic dark-blue color in the joint was observed. Both patients evolved favorably after TKA with excellent results according to the Knee Society Scores (KSS) at three years of follow-up. CONCLUSION: We believe TKA is the right treatment for patients with end-stage disease because it offers considerable relief from pain and allows patients to recover function.

[Ochronosis: A case report]. / Ochronose : une observation.

INTRODUCTION: Ochronosis, also known as alkaptonuria, is a rare autosomal recessive disease. It is caused by a lack of homogentisic acid oxidase, which causes homogentisic acid deposition in the tissues. CASE REPORT: We report a 69-year-old patient who presented with chronic mechanical low back and radicular pain. The clinical examination revealed lumbar lordosis loss, lumbar spinal stiffness, and knee joint limitations of range of motion. On an extra-articular level, the pavilions of the ears and the internal angles of the eyes had a bluish color. Extensive lumbar disc calcifications, vacuum discal phenomenon and osteophytic bridges were demonstrated on standard radiographs of the spine. Clinical and radiographic criteria were used to make the diagnosis of ochronosis. CONCLUSION: Alkaptonuria is a degenerative arthropathy that leads to reduction of functional ability. The use of molecular analysis and genetic research is useful.