[Alkaptonuria: evolution and course of the disease towards ochronotic arthropathy. Series of cases managed with joint replacement]. / Alcaptonuria: evolución y curso de la enfermedad hacia artropatía ocronótica. Serie de casos manejados con reemplazo articular.

INTRODUCTION: alkaptonuria is a very rare metabolic disease with autosomal recessive inheritance due to HGA oxidase deficiency. Classically described and diagnosed in the third to fourth decade of life, affecting both men and women; Its diagnostic impression is clinical based on the blue/black coloration of the conjunctivae, however it is confirmed by the specific analysis of the enzyme in the urine, to date there is no cure and its treatment is palliative and symptomatic. MATERIAL AND METHODS: descriptive, observational, case series study, the primary objective of which is to describe the progression of the disease and its involvement in the musculoskeletal system. RESULTS: two clinical cases are presented in women and men in which the broad clinic is illustrated, its progressive advance and the different alterations that it can generate in the musculoskeletal system. CONCLUSIONS: alkaptonuria is a rare disease which leads to a severe secondary arthropathy, currently without a specific management which is based on treating the symptoms, in its final stages joint replacements are a management option with satisfactory results for the relief of pain.

INTRODUCCIÓN: la alcaptonuria es una enfermedad metabólica inusual, de herencia autosómica recesiva dada por la deficiencia de la oxidasa de HGA. Clásicamente descrita y diagnosticada sobre la tercera a cuarta década de la vida, la cual tiene afectación en ambos sexos, su impresión diagnóstica es clínica, basándose en la coloración azul/negro de las conjuntivas; sin embargo, se confirma mediante el análisis específico de la enzima en la orina, actualmente no existe un tratamiento definitivo, sólo alternativas en cuanto a lo paliativo y sintomático. MATERIAL Y MÉTODOS: estudio descriptivo, observacional, de tipo serie de casos, como objetivo primario se describe la progresión de la enfermedad y su compromiso en el sistema musculoesquelético. RESULTADOS: se presentan dos casos clínicos en mujer y hombre, los cuales ilustran: variedad clínica, avance progresivo y las alteraciones que puede generar en el sistema musculoesquelético. CONCLUSIONES: la alcaptonuria es una enfermedad rara, la cual conlleva una artropatía secundaria severa, sin un tratamiento definitivo dirigido a tratar los síntomas, incluso en sus estadios finales los reemplazos articulares son una opción para proporcionar manejo del dolor obteniendo resultados satisfactorios.

Tale of a Black Heart!

Alkaptonuria is a rare condition of inborn error of metabolism. Association with aortic stenosis has been described; however, diagnosis at the time of valve replacement is infrequent. Recognition of this condition has potential management implications as the durability of prosthetic valves in such cases is unknown. We describe a case report that depicts these unique aspects.

[A male with black cartilage]. / Een man met pijn en zwart kraakbeen.

A 52-year-old men suffered from osteoarthritis of the knee. During knee replacement surgery, the remaining cartilage appeared black. This discoloration and early degeneration of the cartilage is characteristic for the metabolic disorder alkaptonuria in which homogentisic acid accumulates in the body.

[Ochronosis of the Entire Aortic Root in Alkaptonuria;Report of a Case].

Alkaptonuria is a rare hereditary disorder of phenylalanine and tyrosine metabolism, which results in ochronosis of cardiovascular structures including valves, aortic intima, and coronary arteries. Aortic valve disease is the most frequently reported cardiac sequela of alkaptonuria. We report a case of 77-year-old woman with known alkaptonuria who underwent aortic valve replacement for severe aortic stenosis. Operative findings showed impressive ochronosis of the aortic valve and the aortic intima. The post-operative course was uneventful and she was discharged 25 days after the surgery.

Aortic Valve Replacement In Alkaptonuric Ochronosis.

Alkaptonuria is an autosomal recessive inborn error of metabolism of the aromatic amino acids. Deficiency of the homogentisate1,2-dioxygenase leads to an increased blood and urinary concentration of homogentisc acid resulting in a slow accumulation of its oxidation products in the connective tissues (ochronosis). The most common clinical manifestation of ochronosis is arthropathy whereas cardiac involvement is very infrequent. We report the case of a patient with ochronotic involvement of the aortic valve who underwent a valve replacement. Some aspects of pathogenesis, and treatment are discussed.

Clinical and radiological outcomes of total joint arthroplasty in patients with ochronotic arthropathy.

PURPOSE: Alkaptonuria is a rare metabolic disorder, and only a few case reports of total joint arthroplasty (TJA) for ochronotic arthropathy are described in the literature. We aim to analyse the functional and radiological outcomes of TJA in patients with ochronotic arthropathy. METHODS: We retrospectively collected the data of twenty-seven TJA in sixteen patients with ochronotic arthropathy from April 2007 to December 2017. We assessed the functional outcome through pre- and post-operative modified Harris hip score (HHS) and knee society score (KSS). The hip radiographs were analysed for migration and radiolucent zones, and the knee radiographs were assessed using knee society roentgenographic evaluation and scoring system. RESULTS: The mean follow-up was 39.4 months (12-132 months). Two patients died before the final follow-up. There was a statistically significant improvement in mean HHS from 17.8 preoperatively to 78 at the final follow-up (p < 0.001). Similarly, there was a significant improvement in mean KSS, following the surgery, from 27.2 preoperatively to 89.4 (p < 0.001). One patient developed deep infection, and another patient presented with aseptic loosening of the acetabular component after 7 years. In the radiological evaluation at the final follow-up, signs of lysis or loosening were not noted in any of the other patients. CONCLUSION: End-stage arthritis in ochronotic arthropathy is not uncommon. These patients can have multiple joint involvements, and the need for multiple surgeries should be considered. TJA in ochronotic arthropathy leads to a significant improvement in the functional outcome compared with the preoperative disability.

ARTHROPLASTY IN ALKAPTONURIC OCHRONOSIS.

Ochronotic degenerative arthropathy occurs in patients with alkaptonuria. Alkaptonuria disorder is an extremely rare disease characterized by black pigmentation of various tissues (e.g., cartilage and connective tissue). Ochronotic arthropathy is a disabling disease that primarily affects the large joints. Like other metabolic diseases that involve the musculoskeletal system, care must be taken with regard to the quality of the affected bones, tendons and ligaments, and therefore the stability and survival of joint prosthesis. The following is a report of a 66-year-old man affected by several musculoskeletal manifestations of alkaptonuria with severe joints disruption, who was successfully treated with total left hip and total right knee replacements. Surgical, anesthesiological and postoperative management of these patients may require more vigilance due to the associated comorbidities of this disorder.

[Black knee-ochronotic alterations in alkaptonuria]. / Das schwarze Knie ­ ochronotische Veränderungen im Rahmen einer Alkaptonurie.

This article presents the case of a 53-year-old male patient born in Sri Lanka, who presented to the outpatient unit with the suspicion of empyema of the knee joint. Within the framework of knee arthroscopy, the diagnosis of ochronosis was made and later confirmed by histopathological biopsy. The alkaptonuria is caused by a homogentisate 1,2-dioxygenase deficiency and leads to an accumulation of homogentisic acid, a degradation product of tyrosine. This leads to the characteristic appearance of ochronosis with bluish-black deposits in the tissue (e.g. in connective tissue, sclera and ear cartilage) and a black coloration of the urine.

Management of a pseudarthrosis with sagittal malalignment in a patient with ochronotic spondyloarthropathy.

PURPOSE: Ochronotic spondyloarthropathy is an uncommon disease, and its association to sagittal malalignment in the context of a pseudarthrosis has never been described. METHODS: We present the case of a 56-year-old female, who underwent previously L4L5 laminectomy for central canal stenosis and started later on to complain of progressively severe low back pain with a significant forward imbalance while walking. X-rays showed non-compensated sagittal malalignment due to thoracolumbar kyphosis, CT scan revealed multilevel central intradiscal calcifications with important vacuum disc at L4L5, and MRI showed T1 and T2 hypointensity signal at the same level with bone marrow oedema. Alkaptonuric ochronosis was suspected and confirmed by the presence of homogentisic acid in the urine, and the diagnosis of L4L5 pseudarthrosis with associated severe sagittal malalignment in the context of ochronotic spondyloarthropathy was established. RESULTS: The patient underwent surgery with a posterior-only approach with a long-segment pedicle screw construct from T10 to the pelvis with a 360° fusion with a cage at L4L5. Samples taken from the disc and ligaments confirmed the diagnosis of ochronotic spondyloarthropathy macroscopically and microscopically. She could walk on day 2 with a satisfactory clinical and radiological result at 2 years. CONCLUSION: This is the first case in the literature to describe a post-laminectomy pseudarthrosis leading to a significant sagittal malalignment in a patient with ochronotic spondyloarthropathy. Management of such a case is challenging as the spine is partially ankylosed; therefore, a long construct is advisable to avoid ankylosing disorders related complications.

"As Black as Ink": A Case of Alkaptonuria-Associated Myelopathy and a Review of the Literature.

STUDY DESIGN: Case report and literature review. OBJECTIVE: To characterize the rare presentation of myelopathy occurring secondary to alkaptonuria and to evaluate the available evidence regarding its treatment. SUMMARY OF BACKGROUND DATA: Alkaptonuria is an autosomal recessive genetic condition with an estimated incidence of 1 in 250,000 to 1 in 1,000,000 people. Mutation of the enzyme homogentisate 1,2-dioxygenase leads to the production of high levels of homogentisic acid, with subsequent deposition in ligaments, cartilage, and menisci. Involvement of the spine is termed "ochronotic spondyloarthropathy," of which myelopathy is an uncommon presentation. METHODS: We present the case of a 57-year-old man with alkaptonuria-associated myelopathy, who underwent surgical decompression. Ten additional cases were identified in the literature by a systematic search of PubMed and Google Scholar. RESULTS: In a patient presenting with myelopathy, alkaptonuria may be suspected because of medical history, family history, symptoms (including darkened urine, pigmented ear cartilage, and sclera), or radiographic changes, such as multilevel disc collapse, progressive wafer-like disc calcification, extensive osteophyte formation, and spinal deformity. The diagnosis can be confirmed by urine homogentisic acid testing. Of the 11 patients presented here or identified in the literature, 2 were treated nonoperatively, 8 were treated with decompressive spinal surgery, and treatment of the myelopathy was not discussed for 1 patient. In all cases in which outcomes were reported, substantial improvement in the patient's condition was seen. CONCLUSION: Alkaptonuria is a rare cause of myelopathy, but one that clinicians should understand. Although no disease-modifying treatment currently exists for alkaptonuria, the use of symptomatic treatments and, particularly, surgical decompression is recommended to address myelopathy if it develops. LEVEL OF EVIDENCE: 4.

Ochronosis of Mitral Valve and Coronary Arteries.

Cardiac ochronosis is a rare complication of alkaptonuria, a disorder of tyrosine metabolism characterized by a triad of dark urine, pigmentation of tissues, and ochronotic arthropathies. When present, cardiac ochronosis generally affects the aortic valve, resulting in aortic stenosis. More rarely, it may affect the mitral valve and the coronary arteries. This report describes the case of a 67-year-old woman with a history of alkaptonuria with severe ochronosis of the coronary arteries and mitral valve who required coronary artery bypass and mitral valve replacement.

Symptomatic pseudarthrosis in ochronotic spine: case report.

In this study the authors report the first example of spinal pseudarthrosis in a patient with ochronosis, and they describe the application of posterior-only 360° surgery as an alternative approach to combined anterior-posterior surgery in the management of pseudarthrosis of an ankylosed spine, regardless of its etiology. Spinal involvement in ochronosis produces loss of flexibility and ankylosis of thoracic and lumbar segments. Pseudarthrosis is a serious complication of the diseases that present with ankylosis of the spine. However, its occurrence in ochronotic spine has not been reported previously. Evaluation of progressive paraparesis in a 68-year-old man with ochronosis revealed pseudarthrosis at the T11-12 level. Circumferential dural sac decompression, debridement of the disc space, interbody fusion, and screw-rod fixation were all done via a posterior-only approach. Postoperatively the patient exhibited a marked recovery in terms of pain and neurological status. At the 3-month follow-up, he was able to walk independently. Ochronosis should be included in the etiology of pseudarthrosis. With aggravation of back pain and the appearance of neurological deficits in an already stable patient with any ankylosing disease, pseudarthrosis should be suspected. Furthermore, single-stage, 360°, posterior-only surgery may obviate the need for single-stage or staged anterior-posterior surgical intervention in patients with pseudarthrosis of the thoracic and lumbar spine.

Ochronosis as Etiology of Requiring Total Knee Arthroplasty-A Case Series.

Alkaptonuria is a rare hereditary metabolic disorder that leads to the accumulation of homogentisic acid accumulation and weakens the collagen, creating fissuring and articular cartilage degeneration. Therefore, we are reporting a multicenter case series of three patients (four arthroplasties) who presented with signs and symptoms of ochronotic arthropathy-and eventually underwent total knee arthroplasty (TKA)-and provide a review of the current literature on total joint arthroplasty in ochronotic osteoarthritis. Each patient achieved excellent Knee Society Scores (KSS) after at least a five-year follow-up-regardless of receiving cemented or cementless prostheses-and suffered no complications. There have been a number of case reports published on patients who had TKA and were found to have a diagnosis of ochronosis. We believe that surgery for symptomatic patients who are surgical candidates for TKA should not be delayed for concerns of complications. However, future studies should compare outcomes to those who undergo TKA without ochronotic arthropathy.

Alkaptonuria--first inborn error of metabolism known for a century and new treatment option--preliminary report.

Alkaptonuria is a rare inborn error of metabolism, identified over a century ago. But its basic pathomechanism (i.e. ochronosis) is still not completely explained. Though clinical onset of osteoarthropathy and complications from other organs (including: heart and blood vessels, skin, eyes, kidneys) occurs at adult age, the symptoms are progressive, cause severe pains and significantly limit everyday life of the patients. Until now no effective therapeutic methods have been known in alkaptonuria. Recently, thanks to an initiative of the international patient organization for alkaptonuria, a hope for a potential treatment availability, appears. So, alkaptonuria is an example of a role of multidysciplinary care, cooperation and ongoing progress in the area of rare diseases.

Erbium-doped yttrium aluminium garnet ablative laser treatment for endogenous ochronosis.

Ochronosis is a rare disease characterised clinically by bluish-grey skin discolouration and histologically by yellow-brown pigment deposits in the dermis. It occurs in endogenous and exogenous forms. Endogenous ochronosis, also known as alkaptonuria, is an autosomal recessive disease of tyrosine metabolism, resulting in the accumulation and deposition of homogentisic acid in connective tissue. We report a case of facial endogenous ochronosis and coexistent photodamage, which was successfully treated with erbium-doped yttrium aluminium garnet laser resurfacing and deep focal point treatment to remove areas of residual deep pigment.

Aortic valve disease as a first manifestation of Alcaptonuria in surgically treated patient. Case report.

BACKGROUND: Alcaptonuria, a rare metabolic disorder (1:250 000), is usually presented with symptoms such as arthropathies of weight bearing joints. CASE REPORT: In this case, a 65 year old woman was admitted to our hospital with severe aortic stenosis and no other symptoms that would suggest the existance of Alcaptonuria. Intraoperative findings of black discoloration of the affected valve and ascending aorta, pointed towards the diagnosis of cardiac ochronosis, what was then confirmed by a PH examination. CONCLUSION: This case suggests that although alcaptonuria is a slow progressive disease with cardiac ochronosis as a predictable late complication, it can nevertheless be a first sign. In that case the attention should be brought to the surely affected lumbar spine and weight bearing joints, and other connective tissue. KEY WORDS: Alcaptonuria, Aortic valve, Cardiac ochronosis, Surgery.

[Arthropathia ochronotica: a rare cause of early joint degeneration]. / Arthropathia ochronotica: eine seltene ursache frühzeitiger gelenkdegeneration.

HISTORY AND ADMISSION FINDINGS: A 70-year-old deaf-mute women suffered from progressive chronic pain of the right hip joint caused by destructive osteoarthritis of the hip. INVESTIGATIONS: In addition to painfully restricted range of motion of the right hip joint the clinical examination showed a bluish-black pigmentation of the ear-cartilage and the sclera. TREATMENT AND COURSE: A total endoprosthetic replacement of the right hip joint was performed. During surgery, blackening of the hip joint capsule and cartilage was found. Histological, the diagnosis of an ochronosis was confirmed. Discoloration after exposure of urine to air supported the diagnosis. Based on extensive internal medical examination relevant cardiac changes were excluded. CONCLUSION: Ochronosis (arthropathia ochronotica) is a rare entity which can be identified by a visual diagnosis. Early diagnosis can provide crucial information for the prognosis. Additionally, an interdisciplinary treatment concept should be established because of the early onset of degenerative changes at the skeletal system and pathological changes at internal organs. With suspicion on an ochronosis extended internal examinations are recommended in order to avoid complications.

Choice of valve prosthesis in a rare clinical condition: aortic stenosis due to alkaptonuria.

Alkaptonuria is a rare inherited disorder of tyrosine metabolism, which results in deposition of homogentisic acid in the connective tissues. The accumulation of homogentisic acid in connective tissue causes the syndrome known as ochronosis, which is typically manifested by skin pigmentation, degenerative arthropathy and discolouration of urine. Cardiovascular involvement is a much less common complication of alkaptonuria but poses a greater risk to the patient's health. We present the case of a 65 year-old man with aortic stenosis and a previous diagnosis of alkaptonuria who underwent successful aortic valve replacement with a mechanical prosthesis.