Extensive prostatic calculi in a young man should always elicit the suspicion of alkaptonuria.Although prostatic calculi are seen in chronic prostatitis,chronic pelvic pain syndrome and benign prostate hyperplasia,non...Extensive prostatic calculi in a young man should always elicit the suspicion of alkaptonuria.Although prostatic calculi are seen in chronic prostatitis,chronic pelvic pain syndrome and benign prostate hyperplasia,none of these have prostatic calculi or calcification as extensive as in alkaptonuria.A 36 years young man who had severed obstructive lower urinary tract symptoms with extensive prostatic calculi was found to be alkaptonuric on further evaluation.展开更多
Alkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of active enzyme homogentisate 1,2-dioxygenase (HGD). The primary consequence of HGD deficiency is increased circulating homogentisic a...Alkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of active enzyme homogentisate 1,2-dioxygenase (HGD). The primary consequence of HGD deficiency is increased circulating homogentisic acid (HGA), the main agent in the pathology of AKU disease. Here we report the first metabolomic analysis of AKU homozygous Hgd knockout (Hgd−/−) mice to model the wider metabolic effects of Hgd deletion and the implication for AKU in humans. Untargeted metabolic profiling was performed on urine from Hgd−/− AKU (n = 15) and Hgd+/− non-AKU control (n = 14) mice by liquid chromatography high-resolution time-of-flight mass spectrometry (Experiment 1). The metabolites showing alteration in Hgd−/− were further investigated in AKU mice (n = 18) and patients from the UK National AKU Centre (n = 25) at baseline and after treatment with the HGA-lowering agent nitisinone (Experiment 2). A metabolic flux experiment was carried out after administration of 13C-labelled HGA to Hgd−/−(n = 4) and Hgd+/−(n = 4) mice (Experiment 3) to confirm direct association with HGA. Hgd−/− mice showed the expected increase in HGA, together with unexpected alterations in tyrosine, purine and TCA-cycle pathways. Metabolites with the greatest abundance increases in Hgd−/− were HGA and previously unreported sulfate and glucuronide HGA conjugates, these were decreased in mice and patients on nitisinone and shown to be products from HGA by the 13C-labelled HGA tracer. Our findings reveal that increased HGA in AKU undergoes further metabolism by mainly phase II biotransformations. The data advance our understanding of overall tyrosine metabolism, demonstrating how specific metabolic conditions can elucidate hitherto undiscovered pathways in biochemistry and metabolism.展开更多
BACKGROUND Ochronosis,also known as alkaptonuria,is a rare autosomal recessive selfmetabolic disease arising from deficiency of homogentisate 1,2 dioxygenase enzyme.It affects several organs and muscoskeletal structur...BACKGROUND Ochronosis,also known as alkaptonuria,is a rare autosomal recessive selfmetabolic disease arising from deficiency of homogentisate 1,2 dioxygenase enzyme.It affects several organs and muscoskeletal structures.We herein report a case of a patient who presented with severe hip arthropathy complicated with late stage ochronosis.CASE SUMMARY A 56-year-old male patient was admitted in our department in 2019 with complaints of chronic low backache and left hip pain.After the required investigations were done,lumbar disc herniation and severe hip arthritis were the initial diagnosis.A total left hip arthroplasty was performed.Ochronotic osteoarthritis was only obtained post-surgery as confirmatory diagnosis.He was again admitted mid 2022 with the same complaints on the right hip.Subsequently,he underwent a total right hip arthroplasty.Post-operative recovery and follow-ups were deemed very satisfactory.CONCLUSION Ochronosis is an unusual diagnosis for a patient who presents with typical hip arthritis.Thus,unless meticulous history taking and advanced laboratory tests,the diagnosis can easily be missed by surgeons.展开更多
Alkaptonuria is a rare inherited tyrosine metabolism disorder, resulting in homogentisic acid deposition in the connective tissues. The condition is commonly referred to as ochronosis and manifests as skin pigmentatio...Alkaptonuria is a rare inherited tyrosine metabolism disorder, resulting in homogentisic acid deposition in the connective tissues. The condition is commonly referred to as ochronosis and manifests as skin pigmentation, degenerative arthropathy, and black urine. Among the rare complications of this disease is the involvement of the cardiovascular system. We report a case of a 63-year-old woman with alkaptonuric ochronosis who had already undergone three joint replacements. She was referred to our center for aortic valve replacement after accidentally discovering severe aortic valve stenosis in the preoperative assessment prior to her fourth joint replacement. Intraoperative findings included ochronosis of a severely calcified black-pigmented aortic valve and black pigmentation of the aortic intima. Histopathological analysis and elevated homogentisic acid levels in the patient’s urine confirmed the diagnosis of alkaptonuria. However, alkaptonuria was not diagnosed until aortic valve replacement despite the previous symptoms and signs. This report aims to outline the history, etiology, pathogenesis, clinical presentation, and treatment of aortic valve ochronosis in addition to presenting the case.展开更多
BACKGROUND Ochronotic arthropathy(OcA)is a rare disease,which is caused by the accumulation of homogentisic acid in the joint.Patients with OcA have obvious joint pain and the disease progresses rapidly,eventually res...BACKGROUND Ochronotic arthropathy(OcA)is a rare disease,which is caused by the accumulation of homogentisic acid in the joint.Patients with OcA have obvious joint pain and the disease progresses rapidly,eventually resulting in disability.Arthroplasty is an efficacious treatment in patients with OcA.However,when OcA patients have joint infection,is joint replacement an option?In the present report,we performed total knee arthroplasty in a patient with OcA and knee infection under the guidance of one-stage revision theory.CASE SUMMARY A 64-year-old male was referred to our hospital due to severe left knee pain with limited mobility for 2 years.On physical examination,the patient was found to have dark brown pigmentation of the sclera and auricle.Laboratory test results showed elevations in C-reactive protein level(65.79 mg/L)and erythrocyte sedimentation rate(90.00 mm/h).The patient underwent debridement of the left knee joint,during which the cartilage surface of the knee joint was found to be black-brown in color.Bacterial culture of synovial fluid revealed Achromobacter xylosoxidans.We then carried out arthroplasty under the guidance of the theory of one-stage revision.After surgery,the patient’s left knee joint pain disappeared and function recovered without joint infection.CONCLUSION OcA accompanied by joint infection is rare.One-stage revision arthroplasty may be a treatment option for this disease.展开更多
Alkaptonuria （AKU） is an extremely rare autosomal recessive metabolic disorder characterized by a triad of homogentisic aciduria, arthritis, and ochronosis, affecting only 2 5 in a million individuals. The managemen...Alkaptonuria （AKU） is an extremely rare autosomal recessive metabolic disorder characterized by a triad of homogentisic aciduria, arthritis, and ochronosis, affecting only 2 5 in a million individuals. The management of AKU is usually symptomatic. However, surgical intervention necessitates in cases of signiticant arthritis, Here, we presented a 64-year-old female who underwent bilateral total hip and right total knee arthroplasties achieving a successful clinical outcome throughout the 3 years of follow-up.展开更多
文摘Extensive prostatic calculi in a young man should always elicit the suspicion of alkaptonuria.Although prostatic calculi are seen in chronic prostatitis,chronic pelvic pain syndrome and benign prostate hyperplasia,none of these have prostatic calculi or calcification as extensive as in alkaptonuria.A 36 years young man who had severed obstructive lower urinary tract symptoms with extensive prostatic calculi was found to be alkaptonuric on further evaluation.
基金BPN is funded by the University of Liverpool,Royal Liverpool University Hospitals Trust and Agilent Technologies UK Ltd.ASD is funded through a National Institute for Health Research Doctoral Research Fellowship(No.HCS DRF-2014-05-009).
文摘Alkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of active enzyme homogentisate 1,2-dioxygenase (HGD). The primary consequence of HGD deficiency is increased circulating homogentisic acid (HGA), the main agent in the pathology of AKU disease. Here we report the first metabolomic analysis of AKU homozygous Hgd knockout (Hgd−/−) mice to model the wider metabolic effects of Hgd deletion and the implication for AKU in humans. Untargeted metabolic profiling was performed on urine from Hgd−/− AKU (n = 15) and Hgd+/− non-AKU control (n = 14) mice by liquid chromatography high-resolution time-of-flight mass spectrometry (Experiment 1). The metabolites showing alteration in Hgd−/− were further investigated in AKU mice (n = 18) and patients from the UK National AKU Centre (n = 25) at baseline and after treatment with the HGA-lowering agent nitisinone (Experiment 2). A metabolic flux experiment was carried out after administration of 13C-labelled HGA to Hgd−/−(n = 4) and Hgd+/−(n = 4) mice (Experiment 3) to confirm direct association with HGA. Hgd−/− mice showed the expected increase in HGA, together with unexpected alterations in tyrosine, purine and TCA-cycle pathways. Metabolites with the greatest abundance increases in Hgd−/− were HGA and previously unreported sulfate and glucuronide HGA conjugates, these were decreased in mice and patients on nitisinone and shown to be products from HGA by the 13C-labelled HGA tracer. Our findings reveal that increased HGA in AKU undergoes further metabolism by mainly phase II biotransformations. The data advance our understanding of overall tyrosine metabolism, demonstrating how specific metabolic conditions can elucidate hitherto undiscovered pathways in biochemistry and metabolism.
文摘BACKGROUND Ochronosis,also known as alkaptonuria,is a rare autosomal recessive selfmetabolic disease arising from deficiency of homogentisate 1,2 dioxygenase enzyme.It affects several organs and muscoskeletal structures.We herein report a case of a patient who presented with severe hip arthropathy complicated with late stage ochronosis.CASE SUMMARY A 56-year-old male patient was admitted in our department in 2019 with complaints of chronic low backache and left hip pain.After the required investigations were done,lumbar disc herniation and severe hip arthritis were the initial diagnosis.A total left hip arthroplasty was performed.Ochronotic osteoarthritis was only obtained post-surgery as confirmatory diagnosis.He was again admitted mid 2022 with the same complaints on the right hip.Subsequently,he underwent a total right hip arthroplasty.Post-operative recovery and follow-ups were deemed very satisfactory.CONCLUSION Ochronosis is an unusual diagnosis for a patient who presents with typical hip arthritis.Thus,unless meticulous history taking and advanced laboratory tests,the diagnosis can easily be missed by surgeons.
文摘Alkaptonuria is a rare inherited tyrosine metabolism disorder, resulting in homogentisic acid deposition in the connective tissues. The condition is commonly referred to as ochronosis and manifests as skin pigmentation, degenerative arthropathy, and black urine. Among the rare complications of this disease is the involvement of the cardiovascular system. We report a case of a 63-year-old woman with alkaptonuric ochronosis who had already undergone three joint replacements. She was referred to our center for aortic valve replacement after accidentally discovering severe aortic valve stenosis in the preoperative assessment prior to her fourth joint replacement. Intraoperative findings included ochronosis of a severely calcified black-pigmented aortic valve and black pigmentation of the aortic intima. Histopathological analysis and elevated homogentisic acid levels in the patient’s urine confirmed the diagnosis of alkaptonuria. However, alkaptonuria was not diagnosed until aortic valve replacement despite the previous symptoms and signs. This report aims to outline the history, etiology, pathogenesis, clinical presentation, and treatment of aortic valve ochronosis in addition to presenting the case.
基金Supported by Talent Training Project of Guangdong Provincial Bureau of Traditional Chinese Medicine,No.0103030908Guangdong Provincial Hospital of Traditional Chinese Medicine and the School of Biomedicine,Chinese University of Hong Kong School of Medicine,Basic Clinical Collaborative Innovation Project,No.YN2018HK04。
文摘BACKGROUND Ochronotic arthropathy(OcA)is a rare disease,which is caused by the accumulation of homogentisic acid in the joint.Patients with OcA have obvious joint pain and the disease progresses rapidly,eventually resulting in disability.Arthroplasty is an efficacious treatment in patients with OcA.However,when OcA patients have joint infection,is joint replacement an option?In the present report,we performed total knee arthroplasty in a patient with OcA and knee infection under the guidance of one-stage revision theory.CASE SUMMARY A 64-year-old male was referred to our hospital due to severe left knee pain with limited mobility for 2 years.On physical examination,the patient was found to have dark brown pigmentation of the sclera and auricle.Laboratory test results showed elevations in C-reactive protein level(65.79 mg/L)and erythrocyte sedimentation rate(90.00 mm/h).The patient underwent debridement of the left knee joint,during which the cartilage surface of the knee joint was found to be black-brown in color.Bacterial culture of synovial fluid revealed Achromobacter xylosoxidans.We then carried out arthroplasty under the guidance of the theory of one-stage revision.After surgery,the patient’s left knee joint pain disappeared and function recovered without joint infection.CONCLUSION OcA accompanied by joint infection is rare.One-stage revision arthroplasty may be a treatment option for this disease.
文摘Alkaptonuria （AKU） is an extremely rare autosomal recessive metabolic disorder characterized by a triad of homogentisic aciduria, arthritis, and ochronosis, affecting only 2 5 in a million individuals. The management of AKU is usually symptomatic. However, surgical intervention necessitates in cases of signiticant arthritis, Here, we presented a 64-year-old female who underwent bilateral total hip and right total knee arthroplasties achieving a successful clinical outcome throughout the 3 years of follow-up.
