Low serum alkaline phosphatase (sALP)-hypophosphatasemia-is a characteristic of hypophosphatasia (HPP), but related to several clinical conditions. Here, we evaluated the frequency, persistency and the etiology of hypophosphatasemia in children. In retrospective analyses of sALP measurements from children, evaluated according to in-house constructed age- and sex-specific reference ranges, patients with no normal sALP measurement (Unresolved hypophosphatasemia) were invited for reanalysis. Prospectively, ALP substrates, pyridoxal-5-phosphate (PLP), and phosphoethanolamine (PEA) were measured in patients with persistent hypophosphatasemia. Radiographs and ALPL gene sequencing for HPP were performed to the cases with elevated PEA and/or PLP. From 130,340 sALP measurements of 93,162 patients, hypophosphatasemia was detected in 1404 samples from 867 patients (0.9%). Among them, 745 had at least one normal sALP values in laboratory records, grouped as transient hypophosphatasemia. 75 out of 122 patients with unresolved hypophosphatasemia could be reanalyzed for sALP, of whom PLP and PEA measurements were required in 37 due to persistent hypophosphatasemia. Both PEA and PLP were elevated in 4 patients, and ALPL gene analysis showed heterozygous mutations in 3 patients and homozygous in 1 patient. Elevated PEA with normal PLP were detected in 3 patients, and one had a heterozygous ALPL mutation. Anemia was the most common diagnosis, and upper respiratory tract infections and chronic diseases were more common in transient and unresolved hypophosphatasemia, respectively. In conclusion, reflected persistent hypophosphatasemia frequency was 1/1552 (0.06%) in this large pediatric cohort and, ALPL gene mutations were detected in 13.5% (5/37) of the studied cases. Although biochemical hypophosphatasemia is not uncommon, clinically significant HPP is rare.

中文翻译：

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儿童低磷血症的临床意义。

低血清碱性磷酸酶（sALP）-低磷血症-是低磷血症（HPP）的特征，但与几种临床疾病有关。在这里，我们评估了儿童低磷血症的发生频率，持续性和病因。在对儿童sALP测量值进行回顾性分析时，根据内部构建的针对年龄和性别的参考范围进行评估，邀请没有正常sALP测量值（未解决的低血磷）的患者进行重新分析。前瞻性地，在患有持续性低血磷的患者中测量了ALP底物，5-磷酸吡ido醛（PLP）和磷酸乙醇胺（PEA）。对PEA和/或PLP升高的病例进行HPP的放射线照片和ALPL基因测序。根据93,162位患者的130,340 sALP测量结果，在867例患者中的1404个样本中检测到低磷血症（0.9％）。其中，745个在实验室记录中至少具有一个正常的sALP值，归为短暂性低血磷。可以重新分析122例未解决的低磷酸血症患者中的75例sALP，其中37例由于持续的低磷酸血症需要进行PLP和PEA测量。PEA和PLP均升高4例，ALPL基因分析显示3例为杂合突变，1例为纯合。在3例患者中检测到PEA升高且PLP正常，其中1例具有杂合ALPL突变。贫血是最常见的诊断，上呼吸道感染和慢性疾病分别在短暂性和未解决的低磷血症中更为常见。结论，反映出在这个大儿科队列中持续性低血磷频率为1/1552（0.06％），并且在所研究病例的13.5％（5/37）中检测到ALPL基因突变。尽管生化性低磷血症并不少见，但临床意义上的HPP很少见。