Ranganath Lakshminarayan R, Khedr Milad, Vinjamuri Sobhan, Gallagher James A
Department of Clinical Biochemistry & Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK.
Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK.
J Inherit Metab Dis. 2021 May;44(3):666-676. doi: 10.1002/jimd.12363. Epub 2021 Jan 26.
A large alkaptonuria (AKU) cohort was studied to better characterize the poorly understood spondyloarthropathy of rare disease AKU. Eighty-seven patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Seven only attended once. Fifty-seven attended more than once and received nitisinone 2 mg daily. Twenty-three attended at least twice without receiving nitisinone. Assessments included questionnaire analysis, Positron emission tomography computerised tomography (PETCT), as well as photographs of ochronotic pigment in eyes and ears at baseline when 2 mg nitisinone was commenced and yearly thereafter. Blood and urine samples were collected for chemical measurement. The prevalence of ochronosis, as well as pain, PETCT and combined pain and PETCT scores, was greatly increased at 90.5%, 85.7%, 100%, and 100%, respectively. Joint pain scores were greatest in proximal joints in upper and lower limbs. PETCT joint scores were higher in proximal joints in upper limb but higher in distal joints in the lower limb. Spine pain scores were highest in lumbar, followed by cervical, thoracic, and cervical regions at 77.4%, 59.5%, 46.4%, and 25%, respectively. PETCT spine scores were highest in thoracic followed by lumbar, cervical, and sacroiliac regions at 74.4%, 70.7%, 64.6%, and 47.8% respectively; ochronosis associated closely with spondyloarthropathy scores (R = .65; P < .0001). Nitisinone reversed ochronosis significantly, with a similar pattern of decreased joint and spine disease. Spondyloarthropathy is a highly prevalent feature in this NAC cohort. Ochronosis appears to be associated with spondyloarthropathy. Nitisinone decreases ochronosis and had a similar nonsignificant effect pattern on spondyloarthropathy.
为了更好地描述罕见病黑尿症（AKU）中人们了解较少的脊柱关节病特征，对一个大型黑尿症队列进行了研究。2007年至2020年间，87名患者前往国家黑尿症中心（NAC）就诊。其中7人仅就诊过一次。57人多次就诊并接受每日2毫克的尼替西农治疗。23人至少就诊过两次但未接受尼替西农治疗。评估包括问卷调查分析、正电子发射断层扫描计算机断层扫描（PETCT），以及在开始服用2毫克尼替西农时的基线水平以及此后每年对眼睛和耳朵中褐黄病色素的拍照。采集血液和尿液样本进行化学测量。褐黄病以及疼痛、PETCT以及疼痛与PETCT综合评分的患病率分别大幅上升至90.5%、85.7%、100%和100%。关节疼痛评分在上下肢近端关节中最高。PETCT关节评分在上肢近端关节中较高，但在下肢远端关节中较高。脊柱疼痛评分在腰椎最高，其次是颈椎、胸椎和骶椎，分别为77.4%、59.5%、46.4%和25%。PETCT脊柱评分在胸椎最高，其次是腰椎、颈椎和骶髂关节区域，分别为74.4%、70.7%、64.6%和47.8%；褐黄病与脊柱关节病评分密切相关（R = 0.65；P < 0.0001）。尼替西农显著逆转了褐黄病，关节和脊柱疾病也有类似的下降模式。脊柱关节病是该NAC队列中非常普遍的特征。褐黄病似乎与脊柱关节病有关。尼替西农可减轻褐黄病，并对脊柱关节病有类似的非显著影响模式。
