[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.

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.

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.

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.

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.

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.

[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.

[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.

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.

"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.

Alkaptonuria--a review of surgical and autopsy pathology.

Alkaptonuria is a rare, inherited defect of homogentisic acid 1,2-dioxygenase that leads to the widespread deposition of polymeric homogentisic acid, and clinical symptoms from degeneration of joints and the aortic valve. Pathological descriptions are few and mainly those of late-stage changes related to joint or valve failure. In this review, the macroscopic and histopathological changes in the tissues in alkaptonuria are illustrated by the detailed autopsy study of a 74-year-old female who died from disseminated ovarian carcinoma. The pathology is discussed in the context of the literature and in relation to potential pathogenic mechanisms of tissue damage. This review highlights the heterogeneity of some of the manifestations. In symptomatic patients, degenerative changes in synovial and intervertebral joints are usually well advanced, while early changes include diffuse cartilage pigmentation and chondrocyte necrosis. The initial stage of pigment deposition in the cardiovascular system may be influenced by intravascular pressure and flow disturbances, whereas more intense pigmentation affects fibrolipid components of atheromatous plaques. Pigmentation of the aortic and mitral valve cusps and valve rings is a result of intracellular and extracellular pigment deposition and is associated with calcification and clinically significant aortic stenosis.

Surgical Management in Cervical Spondylotic Myelopathy Due to Alkaptonuria.

BACKGROUND: Ochronotic arthropathy related to alkaptonuria is a rare condition. Cervical spine involvement with myelopathic features has been even more rarely described, particularly related to atlantoaxial instability. As such, little is known about the optimal surgical management in these patients. CASE DESCRIPTION: We described the first case, to our knowledge, of a patient with alkaptonuria and related cervical spondylotic myelopathy from pannus formation at the atlantoaxial joint. We describe our choices in surgical management of this rare condition in a patient with an excellent outcome. CONCLUSION: Ochronotic cervical spondylotic myelopathy is a rare condition and may require additional considerations in surgical treatment compared to more common causes of cervical spondylotic myelopathy. In our case, we elected for decompression with posterior occipitocervical screw fixation and were able to achieve neurologic recovery with no complications, currently at 2-year follow-up.

Orthopaedic problems in patients affected by alkaptonuria. A case report.

Alkaptonuria is a rare congenital metabolic disorder. A defect of the enzyme homogentisic oxidase results in a block of the metabolic pathway of the amino acids phenylalanine and tyrosine. Deposits of homogentisic acid polymers in connective tissue cause various organ manifestations, including musculoskeletal symptomatology. A 66 year-old woman was twice admitted to our Department because of progressive knee and low back pain. Physical examination and accessory investigations confirmed that her various complaints were caused by underlying alkaptonuria. We use this case and a review of literature to discuss orthopaedic problems in patients with alkaptonuria and describe the cardinal signs and symptoms of this disease, its diagnosis and treatment.

A case of alkaptonuria with root canal stenosis.

Spinal involvement in alkaptonuria is common. Patients usually present in the third or fourth decade with spondylosis or acute intervertebral disc prolapse. Alkaptonuria with root canal stenosis has however hitherto not been reported. We wish to report one such patient.

[Alkaptonuria and ochronotic arthropathy. Arthroscopic and intraoperative findings in implantation of a knee joint surface replacing prosthesis]. / Alkaptonurie und ochronotische Arthropathie. Arthroskopischer und intraoperativer Befund bei Implantation einer oberflächenerneuernden Knieendoprothese.

Alcaptonuria is a rare (incidence approx. 1:10(6)), autosomal-recessive transmitted metabolic disease. The basic defect is a lack of the enzyme homogentisic acid oxidase. During metabolism of phenylalanin and tyrosin to fumaric acid and acetoacetic acid this enzymatic defect causes an accumulation of the intermediate breakdown product homogentisic acid in bradytrophic tissues resulting in pigmentation and calcification of the intervertebral disks. We present a 57 year old female patient in whom we diagnosed alcaptonuria by the appearance of the typical symptom trias homogentisic acid excretion in the urine, ochronosis and arthritis. The anamnesis and results of a knee arthroscopy, radiographic and laboratory examinations as well as the intraoperative and histological findings during implantation of a knee joint surface replacing prosthesis (Gemini-System, Link Co., Hamburg, Germany) are reported.

Shoulder arthroplasty in alkaptonuric arthropathy: a clinical case report and literature review.

Alkaptonuria is a rare hereditary metabolic disease of autosomal recessive inheritance, resulting from deficiency of the enzyme homogentisic acid oxidase. The term "alkaptonuria" was first used in 1859 by Boedeker to describe a patient's urinary reducing compound, and in 1866, Virchow coined the term "ochronosis" due to typical yellow pigmentation. Deposition of this pigment in articular cartilage leads to ochronotic arthropathy, the most incapacitating complication of alkaptonuria. We report a rare case of shoulder ochronotic arthritis, treated with total shoulder arthroplasty, achieving a successful long-term clinical and radiological outcomes.

Ochronotic arthropathy: diagnosis and management: a critical review.

Alkaptonuria, a rare hereditary metabolic disorder, is characterized by accumulation of homogentisic acid in the connective tissues resulting from lack of the enzyme homogentisic acid oxidase. Ochronosis, dark pigmentation of connective tissues, is the musculoskeletal manifestation of alkaptonuria. In this article, we report the case of a 53-year-old man who had ochronotic arthropathy and advanced degenerative changes in the shoulders managed with bilateral total shoulder arthroplasty. Three-year follow-up results were satisfactory: good range of motion, no pain, and no signs of prosthesis loosening. Shoulder function was significantly improved after surgery, as documented by Constant scores. This case suggests that shoulder prosthesis results are not affected by alkaptonuria.