Clinical spectrum of hypophosphatasia diagnosed in adults
Clinical spectrum of hypophosphatasia diagnosed in adults
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DOI：
10.1016/j.bone.2013.01.024
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发表时间：
2013-05-01
期刊：
影响因子：
4.1
通讯作者：
Wermers, Robert A.
中科院分区：
文献类型：
--
作者：
Berkseth, Kathryn E.;Tebben, Peter J.;Wermers, Robert A.
在成人中诊断的低磷酸酶症（HPP）表现出广泛的临床表现，其中许多是非特异性的。我们试图通过对1976年至2008年诊断为HPP的马约诊所罗切斯特成人患者的评价来评估成人HPP的临床特征。受试者通过诊断代码或医疗记录识别。入选标准为诊断时年龄≥ 18岁;低血清碱性磷酸酶（AP），无双膦酸盐治疗;和一个额外的因素：吡哆醛5 '-磷酸（PLP）或尿磷酸乙醇胺（PEA）升高，骨软化症的证据，或家族史。由于缺乏前瞻性的标准化临床评估和基因检测，我们无法区分显性携带者和沉默的未受影响的携带者。HPP在22名无关成人中被诊断出（中位年龄49岁; 68%为女性）。大多数患者（68%）在就诊时有症状，包括肌肉骨骼疼痛（41%）或意外骨折（18%）。54%的患者有骨折史：髋关节/股骨颈（23%）、足部（23%，均为女性）、腕关节（18%）和脊柱（9%，均为男性）。9例患者（36%）有多发性骨折，4例（均为女性）有股骨转子下骨折。影像学软骨钙质沉着症（27%）和记录的焦磷酸盐关节病（14%）仅见于女性。中位最低血清AP低于正常下限43%。15/16例患者（94%）尿PEA升高。PLP中位数为68 μ g/L（正常，5-50 μ g/L），所有患者（n = 8）均高于正常值。有症状的受试者有更多的骨折和软骨钙质沉着症，较低的平均最低AP和PLP和较高的平均PEA水平。骨折患者更常见的临床特征包括就诊时的症状、儿童佝偻病史、牙齿异常、较低的平均最小AP和PLP以及较高的平均尿PEA。4例受试者行髂嵴骨活检，2/4的标本符合骨软化。这些结果表明，成人HPP表现出广泛的临床表现，包括肌肉骨骼疼痛，骨折，软骨钙质沉着症和牙齿异常与一些重叠的实验室特征的关系，疾病的严重程度。除了遗传和环境因素外，性别也可能影响HPP的临床表达。(C)2013 Elsevier Inc. All rights reserved.
The presentation of hypophosphatasia (HPP) diagnosed in adults demonstrates a wide range of clinical manifestations, many of which are nonspecific. We sought to assess clinical characteristics of adult HPP by evaluation of Mayo Clinic Rochester adults diagnosed with HPP from 1976 through 2008. Subjects were identified by diagnostic code or medical records. Inclusion criteria were age >= 18 years at diagnosis; low serum alkaline phosphatase (AP) without bisphosphonate therapy; and one additional element: elevated pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), evidence of osteomalacia, or family history. We were unable to distinguish manifesting carriers from silent unaffected carriers due to lack of a prospective standardized clinical evaluation and the absence of genetic testing. HPP was diagnosed in 22 unrelated adults (median age 49 years; 68% women). Most patients (68%) were symptomatic at presentation with features including musculoskeletal pain (41%) or incident fracture (18%). A history of fracture was present in 54%: hip/femoral neck (23%), feet (23%, all women), wrist (18%), and spine (9%, all men). Nine patients (36%) had multiple fractures while 4 (all women) had subtrochanteric femur fractures. Radiographic chondrocalcinosis (27%) and documented pyrophosphate arthropathy (14%) were only observed in women. Median minimum serum AP was 43% below the lower normal limit. Urine PEA was elevated in 15/16 patients (94%). PLP median was 68 mu g/L (normal, 5-50 mu g/L) and all (n = 8) were above normal. Symptomatic subjects had more fractures and chondrocalcinosis, lower median minimum AP and PLP and higher median PEA levels. Clinical features more common in fracture patients included symptoms at presentation, history of childhood rickets, dental abnormalities, lower median minimum AP and PLP, and higher median urine PEA. Four subjects had iliac crest bone biopsies, with 2/4 specimens consistent with osteomalacia.These results suggest that adult HPP demonstrates a wide spectrum of clinical manifestations including musculoskeletal pain, fractures, chondrocalcinosis and dental anomalies with some overlap in laboratory characteristics in relationship to disease severity. In addition to genetic and environmental factors, gender may influence the clinical expression of HPP. (C) 2013 Elsevier Inc. All rights reserved.