Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestraße 59, 22529, Hamburg, Germany.
Department of Orthopaedic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
Osteoporos Int. 2017 Sep;28(9):2653-2662. doi: 10.1007/s00198-017-4087-z. Epub 2017 May 25.
In this study, we report on clinical, radiographic and biochemical characteristics of 38 patients with adult hypophosphatasia. High-resolution peripheral quantitative computed tomography showed alterations of bone microstructure in a subgroup of 14 patients. Pyridoxal-5-phosphate levels correlated with the occurrence of fractures and the number of symptoms.
Hypophosphatasia (HPP) is a rare disorder with a wide range of clinical manifestations. A reduced enzymatic activity of alkaline phosphatase (ALP) is the key marker of the disease, causing an accumulation of ALP substrates such as pyridoxal-5-phosphate (PLP). The purpose of this retrospective study was to further characterize adult onset HPP.
We assessed clinical, radiographic and laboratory characteristics of 38 adult patients with HPP. Diagnosis of HPP was established by the combination of low-serum ALP, raised PLP levels and typical symptoms and was genetically confirmed in 32 patients. Dual-energy X-ray absorptiometry (DXA) and laboratory data were available in most patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed in 14 patients.
Clinical characteristics included a wide spectrum of symptoms. A history of fracture was present in 15 patients (39%). Twenty-one patients (55%) complained about recurring headaches, 23 patients (61%) had recurring muscle pain, 4 patients (11%) suffered from severe muscle weakness and 18 patients (47%) showed dental abnormalities. Z-scores assessed by DXA were only slightly reduced in most adult HPP patients. HR-pQCT of 14 patients showed microstructural changes of trabecular and cortical bone compared to reference values of healthy subjects. The occurrence of fractures and multiple symptoms (>2 typical HPP symptoms) were associated with significantly elevated levels of PLP.
Adult HPP presents with a wide range of clinical symptoms and is not associated with low bone mass in general. PLP seems to be a good marker for disease severity in adult patients as its level is correlated with the occurrence of fractures and number of symptoms.
本研究报告了 38 例成人低磷酸酯酶症患者的临床、放射学和生化特征。高分辨率外周定量计算机断层扫描显示了 14 例患者亚组的骨微观结构改变。吡哆醛-5-磷酸（PLP）水平与骨折发生和症状数量相关。
低磷酸酯酶症（HPP）是一种临床表现广泛的罕见疾病。碱性磷酸酶（ALP）活性降低是该病的关键标志物，导致 ALP 底物如吡哆醛-5-磷酸（PLP）的积累。本回顾性研究的目的是进一步描述成人发病的 HPP。
我们评估了 38 例成人 HPP 患者的临床、放射学和实验室特征。通过组合低血清 ALP、升高的 PLP 水平和典型症状诊断 HPP，在 32 例患者中进行了基因确认。大多数患者均有双能 X 射线吸收仪（DXA）和实验室数据。对 14 例患者进行了高分辨率外周定量计算机断层扫描（HR-pQCT）。
临床特征包括广泛的症状。15 例患者（39%）有骨折史。21 例患者（55%）有反复发作的头痛，23 例患者（61%）有反复发作的肌肉疼痛，4 例患者（11%）有严重的肌肉无力，18 例患者（47%）有牙齿异常。大多数成人 HPP 患者的 DXA 评估 Z 分数仅略有降低。14 例患者的 HR-pQCT 显示与健康受试者参考值相比，小梁和皮质骨的微观结构发生变化。骨折的发生和多种症状（>2 种典型的 HPP 症状）与 PLP 水平显著升高相关。
成人 HPP 表现出广泛的临床症状，总体上与低骨量无关。PLP 似乎是成人患者疾病严重程度的良好标志物，因为其水平与骨折发生和症状数量相关。
