Clinical Analysis Unit, University Hospital Clínico San Cecilio, 18016 Granada, Spain.
Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain.
Int J Mol Sci. 2021 Apr 21;22(9):4303. doi: 10.3390/ijms22094303.
Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5'-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients.
低磷酸酯酶症（HPP）是一种罕见的遗传性疾病，其特征是组织非特异性碱性磷酸酶（TNSALP）活性降低。TNSALP 由 基因编码，该基因在骨骼、肝脏、肾脏和正在发育的牙齿中大量表达。HPP 表现出高度的临床变异性，主要是由于 基因的高度等位基因异质性。HPP 的特征是多系统并发症，尽管最常见的临床表现是骨骼、肌肉和牙齿发生的那些。这些并发症主要是由于无机焦磷酸盐（PPi）和吡哆醛-5'-磷酸（PLP）的积累。已经观察到，该疾病的轻度形式的患病率超过严重形式的 40 倍。HPP 患者至少在 基因中存在一个突变。然而，已知还有其他原因会导致碱性磷酸酶（ALP）水平降低，而 基因中没有突变。尽管在 HPP 中表型可以与基因型相关联，但不能完全确定从基因型预测表型。HPP 特异性酶替代疗法的出现无疑代表了治疗策略的进步，尤其是在儿科患者的严重疾病形式中。
