Whyte M P, Murphy W A, Fallon M D
Am J Med. 1982 Apr;72(4):631-41. doi: 10.1016/0002-9343(82)90474-0.
Three sisters, each with chondrocalcinosis/arthropathy, are described who have the clinical, laboratory and pathologic findings characteristic of the adult form of hypophosphatasia. Premature loss of adult teeth, arthralgias and pain from bilateral femoral pseudo-fractures were associated with subnormal circulating alkaline phosphatase levels, phosphoethanolaminuria and osteomalacia diagnosed by iliac crest biopsy. Assay of alkaline phosphatase activity in the blood of kindred members revealed hypophosphatasemia in one of two younger brothers. Several subjects in subsequent generations also had suspiciously low alkaline phosphatase activity, but did not have histories of significant dental, bone or joint disease. Review of the medical records of the sisters' parents, aunts and uncles revealed normal alkaline phosphatase levels in their father and five of his siblings, but consistently low levels in their mother and two of her siblings. Despite hypophosphatasemia, the sisters' mother and her siblings lived to old age without clinical or radiographic evidence of bone disease. Our findings suggest that although adult hypophosphatasia can be transmitted as a dominant trait in some kindreds, there is considerable variation in the clinical expression of the biochemical defect. One person, generation or family may manifest clinical bone disease and arthropathy whereas the biochemical defect may be present but remain asymptomatic in others. Furthermore, in some cases, the adult form of hypophosphatasia may represent a developmental disorder with hypophosphatasemia appearing during adulthood.
本文描述了三姐妹，她们均患有软骨钙质沉着症/关节病，具备成人型低磷酸酯酶症的临床、实验室及病理特征。恒牙过早脱落、关节痛以及双侧股骨假性骨折引起的疼痛，与循环碱性磷酸酶水平低于正常、磷酸乙醇胺尿症以及通过髂嵴活检诊断出的骨软化症相关。对亲属血液中碱性磷酸酶活性的检测显示，两个弟弟中的一个存在低磷酸酯酶血症。后代中的几名受试者碱性磷酸酶活性也可疑偏低，但并无明显的牙齿、骨骼或关节疾病史。查阅姐妹俩父母、姑姑和叔叔的病历发现，她们父亲及其五个兄弟姐妹的碱性磷酸酶水平正常，但其母亲及其两个兄弟姐妹的水平一直偏低。尽管存在低磷酸酯酶血症，但姐妹俩的母亲及其兄弟姐妹都活到了高龄，没有骨病的临床或影像学证据。我们的研究结果表明，尽管成人型低磷酸酯酶症在某些家族中可作为显性性状遗传，但生化缺陷的临床表型存在相当大的差异。一个人、一代人或一个家族可能表现出临床骨病和关节病，而生化缺陷可能存在但在其他人中无症状。此外，在某些情况下，成人型低磷酸酯酶症可能是一种发育障碍，低磷酸酯酶血症在成年期出现。
