Lawrence John E, Saeed Danish, Bartlett Jonathan, Carrothers Andrew D
Department of Orthopaedics and Trauma, Addenbrooke's Hospital, Cambridge, UK.
Clin Cases Miner Bone Metab. 2017 Sep-Dec;14(3):347-353. doi: 10.11138/ccmbm/2017.14.3.347. Epub 2017 Dec 27.
We report the case of a 55-year-old woman who presented to the emergency department having woken from sleep with right sided thigh swelling. Pelvic radiographs revealed bilateral atypical subtrochanteric femoral fractures (ASFFs). In the two years leading up to this admission, the patient had experienced gradually increasing pain and weakness in her legs which had resulted in a decrease in her mobility from fully mobile to bed-bound. During this time a neurologist had organised a magnetic-resonance imaging (MRI) scan of the brain and spine which was normal. There was no history of bisphosphonate (BP) use. Historical and admission blood tests revealed a persistently low serum alkaline phosphatase (ALP), with all other results within normal limits. The patient was treated with intramedullary nailing of both femurs and histological analysis of bone reamings were characteristic of hypophosphatasia (HPP). The patient was independently mobilising with a walking frame on discharge. Subsequent genetic testing revealed bi-allelic pathogenic variants in the TNSALP gene: c.526G>A, p.(Ala176Thr) and c.1171C>T, p.(Arg391Cys). HPP is an inborn error in metabolism caused by mutation in the gene coding for tissue non-specific alkaline phosphatase (TNSALP), resulting in a decrease in serum ALP concentrations. The age at which it presents which can vary from childhood to middle age, with symptoms ranging from perinatal death to late-onset osteomalacia. In those patients who survive to adulthood, there is a predisposition to fractures, including ASFFs. Treatment with asfotase alfa (a bone-targeted, recombinant human TNSALP) has been approved for perinatal, infantile and paediatric-onset hypophosphatasia. This case emphasises the importance of viewing persistent low ALP as a 'red flag' in patients presenting with musculoskeletal symptoms. Timely diagnosis and treatment of HPP can reduce the risk of serious complications, such as those experienced by this patient.
我们报告了一例55岁女性病例，该患者因右侧大腿肿胀从睡眠中醒来后前往急诊科就诊。骨盆X线片显示双侧非典型转子下股骨骨折（ASFFs）。在此次入院前的两年里，患者腿部疼痛和无力逐渐加重，导致其活动能力从完全可活动下降至卧床不起。在此期间，神经科医生安排了脑部和脊柱的磁共振成像（MRI）扫描，结果正常。患者无使用双膦酸盐（BP）的病史。既往及入院时的血液检查显示血清碱性磷酸酶（ALP）持续偏低，其他所有结果均在正常范围内。患者接受了双侧股骨髓内钉固定治疗，骨钻屑的组织学分析显示为低磷性佝偻病（HPP）特征。患者出院时可借助步行架独立活动。随后的基因检测显示TNSALP基因存在双等位基因致病性变异：c.526G>A，p.（Ala176Thr）和c.1171C>T，p.（Arg391Cys）。HPP是一种先天性代谢缺陷，由编码组织非特异性碱性磷酸酶（TNSALP）的基因突变引起，导致血清ALP浓度降低。其发病年龄可从儿童期到中年不等，症状从围产期死亡到迟发性骨软化症。在存活至成年的患者中，易发生骨折，包括ASFFs。阿法骨化醇（一种靶向骨骼的重组人TNSALP）已被批准用于治疗围产期、婴儿期和儿童期发病的低磷性佝偻病。该病例强调了将持续低ALP视为有肌肉骨骼症状患者的“警示信号”的重要性。及时诊断和治疗HPP可降低严重并发症的风险，如该患者所经历的并发症。
