Hypophosphatasia (HPP) is the metabolic bone disease caused by loss-of-function mutation(s) of the ALPL gene that encodes the cell-surface tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). In HPP, extracellular accumulation of inorganic pyrophosphate (PPi), a TNSALP natural substrate and inhibitor of biomineralization, often leads to rickets or osteomalacia despite normal or sometimes elevated circulating levels of calcium (Ca) and inorganic phosphate (Pi). We report an infant girl with vitamin D deficiency rickets subsequently healed by cholecalciferol administration alone before receiving TNSALP-replacement therapy for accompanying HPP. Throughout her clinical course, circulating Ca and Pi levels were normal or elevated. At presentation with failure-to-thrive at age six months, radiographs revealed severe rickets and serum 25(OH)D was 8 ng/mL (Nl, 30-100), yet low ALP activity 55 U/L (Nl, 124-341), normal Ca 9.3 mg/dL (Nl, 8.5-10.1) and Pi 6.4 mg/dL (Nl, 3.5-7.0), and low-normal parathyroid hormone 21 pg/mL (Nl, 14-72) were instead consistent with HPP. At age nine months, after 1000 IU of cholecalciferol orally each day for six weeks, serum 25(OH)D was 86 ng/mL, strength markedly better, and radiographs documented significant improvement of rickets. At age 18 months, with fully healed vitamin D deficiency rickets, findings of underlying HPP included a waddling gait and Gower sign, metaphyseal "tongues" of radiolucency, elevated serum pyridoxal 5'-phosphate 121 ng/mL (Nl, 2-33), and bi-allelic ALPL missense mutations. Then, nearly complete restoration of strength and radiographic healing of her remaining skeletal disease from HPP occurred during asfotase alfa enzyme replacement treatment. At no time, including presentation, were circulating Ca or Pi levels compromised. Instead, and in keeping with HPP, high-normal or elevated serum Ca and Pi concentrations were consistently documented. Thus, our findings suggest some role for vitamin D in musculoskeletal health beyond assuring circulating mineral sufficiency.

中文翻译：

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维生素 D 缺乏性佝偻病的治愈表明，维生素 D 在肌肉骨骼健康中的作用超出了循环矿物质的充足性

低磷酸酯酶症 (HPP) 是由 ALPL 基因功能丧失突变引起的代谢性骨病，该基因编码细胞表面组织非特异性碱性磷酸酶同工酶 (TNSALP)。在 HPP 中，无机焦磷酸盐 (PPi)（一种 TNSALP 天然底物和生物矿化抑制剂）的细胞外积聚经常导致佝偻病或骨软化，尽管钙 (Ca) 和无机磷酸盐 (Pi) 的循环水平正常或有时升高。我们报告了一名患有维生素 D 缺乏性佝偻病的女婴，随后在接受伴随 HPP 的 TNSALP 替代疗法之前仅通过胆钙化醇给药治愈。在她的整个临床过程中，循环 Ca 和 Pi 水平正常或升高。在六个月大时无法茁壮成长，X 光片显示严重佝偻病，血清 25(OH)D 为 8 ng/mL (Nl, 30-100)，但 ALP 活性低 55 U/L (Nl, 124-341)，正常 Ca 9.3 mg/dL (Nl, 8.5 -10.1) 和 Pi 6.4 mg/dL (Nl, 3.5-7.0) 和低正常甲状旁腺激素 21 pg/mL (Nl, 14-72) 相反与 HPP 一致。在 9 个月大时，每天口服 1000 IU 胆钙化醇，持续 6 周后，血清 25(OH)D 为 86 ng/mL，强度明显好转，X 光片显示佝偻病有显着改善。在 18 个月大时，维生素 D 缺乏性佝偻病完全愈合，潜在 HPP 的发现包括蹒跚步态和 Gower 征、干骺端“舌”透亮、血清 5'-磷酸吡哆醛升高 121 ng/mL (Nl, 2-33)和双等位基因 ALPL 错义突变。然后，在 asfotase alfa 酶替代治疗期间，她的 HPP 剩余骨骼疾病几乎完全恢复了力量和放射影像学愈合。在任何时候，包括演示，循环 Ca 或 Pi 水平都没有受到影响。取而代之的是，与 HPP 一致，血清 Ca 和 Pi 浓度正常或升高的情况一直被记录。因此，我们的研究结果表明，除了确保循环矿物质充足之外，维生素 D 在肌肉骨骼健康中的作用。