Hypophosphataemic Osteomalacia with Complete Recovery
Hypophosphataemic Osteomalacia with Complete Recovery
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低磷血症性骨软化症完全康复
DOI：
10.1136/bmj.1.5399.1672-a
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发表时间：
1964
影响因子：
--
通讯作者：
M. Friedman
中科院分区：
文献类型：
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作者：
C. Dent;M. Friedman
最初对与低磷血症相关的耐药佝偻病的描述来源于对一名有14年佝偻病病史的16岁男孩的详细研究（Albright, Butler, and Bloomberg, 1937）。这名患者的骨病对足够剂量的维生素D治疗传统膳食佝偻病无效。佝偻病的治愈最终是通过每天服用45万国际单位（11.25毫克）的维生素D来实现的。这项研究提出了在某些类型的佝偻病中出现“维生素D抗性”的概念。在过去的25年里，对这类患者进行了大量的研究，很明显，这涉及到一组相关的疾病。低磷血症伴正常钙血症和碱性磷酸酶升高是血浆生化的特征，没有其他生化异常。特别重要的是，该疾病中肾磷酸盐阈值降低，这使得人们认为该疾病可能主要是一种特殊的肾小管功能障碍（Robertson, Harris, and McCune, 1942），尽管其可能是由于继发性甲状旁腺功能亢进的一种形式，但绝不排除这种可能性。随着人们认识到低磷血症性佝偻病可能与各种其他肾小管缺陷有关，其中一些异常是由基因决定的，对肾小管概念的进一步证据也逐渐出现。这些事实导致人们试图根据肾小管功能障碍对这类疾病进行分类（Dent, 1952; Fanconi and Girardet, 1952; Jackson and Linder, 1953; Fraser and Slater, 1958）。区分不同类型的重要性在于它们可能有不同的治疗和预后。在临床实践中，还可以预见到管状缺陷的进一步排列和组合。例如，我们最近研究了两例佝偻病和肾小管缺陷（钙、磷酸盐、氨基酸和蛋白质的再吸收）的患者（Dent和Friedman， 1964），这些肾小管异常的组合不包括在任何原始分类中。低磷血症佝偻病最常见的形式通常表现在6个月至2岁之间。男性儿童比女性受影响更严重，常染色体性连锁基因可以解释该病的强烈遗传模式（Winters, Graham, Williams, McFalls, and Burnett, 1958）。然而，大约三分之一的病例没有家族病史，被认为是由于基因突变引起的（Dent和Harris, 1956; Burnett, Dent, Harper, and Warland, 1964）。在青春期和成年期确诊的患者通常可以提供一些可追溯到童年时期的疾病特征的病史。例如，他们可能会表现出侏儒症，伴有典型的脊柱畸形和明显的长骨相对缩短。肾功能正常，但磷酸盐清除率高。与上述最常见的耐药佝偻病形式相反，一些作者描述了一种进一步的变体，可区分为
The original description of resistant rickets associated with hypophosphataemia was derived from detailed studies on a 16-year-old boy with a 14-year history of rickets (Albright, Butler, and Bloomberg, 1937). The bone disease in this patient failed to respond to a dose of vitamin D adequate to cure classical dietary rickets. Healing of the rickets was eventually obtained by the administration of enormous doses, 450,000 IU (11.25 mg.), of vitamin D daily. This study gave rise to the concept of" vitamin D resistance" occurring in certain types of rickets.In the course of the past 25 years numerous studies have been made on this type of patient, and it is clearthat a group of related diseases are involved. It has been shown that hypo-phosphataemia associated with normocalcaemia and a raised alkaline phosphatase was characteristic of the plasma biochemistry, no other biochemical abnormalities being present. Of particular importance has been the demonstration of a lowered renal phosphate threshold in this disease, which has led to suggestions that the disease may be primarily one of a specific renal tubular dysfunction (Robertson, Harris, and McCune, 1942), although the possibility of its being due to a form of secondary hyperparathyroidism is by no means yet excluded. Additional evidence for the tubular concept has been forth-coming with the recognition that hypophosphataemic rickets could be associated with various other tubular defects, some of these abnormalities being genetically determined. These facts led to an attempt to classify this group of diseases on the basis of the disorder of renal tubular function present (Dent, 1952; Fanconi and Girardet, 1952; Jackson and Linder, 1953; Fraser and Slater, 1958). The importance of distinguishing the various types lies in the fact that they may have a different treatment and prognosis. It was also to be expected that further permutations and combinations of tubular defects would be met in clinical practice. We have, for instance, recently studied two patients with rickets and a renal tubular defect for thereabsorp-tion of calcium, phosphate, amino-acids, and protein (Dent and Friedman, 1964), a combination of renal tubularabnormalities not included in any of the original classifications. The commonest form of hypophosphataemic rickets manifests itself usually between 6 months and 2 years of age. Male children are more severely affected than females and an auto-somal sex-linked gene can be implicated to explain the strong hereditary pattern of the disease (Winters, Graham, Williams, McFalls, and Burnett, 1958). However, approximately one-third of cases present without a family history of the disease and are believed to be due to a gene mutation (Dent and Harris, 1956; Burnett, Dent, Harper, and Warland, 1964). Patients diagnosed in adolescence and adulthood can usually give a history of some features of the disease going back to childhood. For instance, they are likely to show dwarfism with typical rachitic deformities and marked relative shortening of the long bones. Renal function is normal except that a high clearance for phosphate can be demonstrated. In contrast to the above commonest form of resistant rickets, some authors have described a further variant distinguishable by