Hypophosphatasia: A Unique Disorder of Bone Mineralization Villa Suárez, Juan Miguel García Fontana, Cristina Andujar Vera, Francisco González Salvatierra, Sheila Haro Muñoz, Tomás de Contreras Bolívar, Victoria García Fontana, Beatriz Muñoz Torres, Manuel Eduardo Hypophosphatasia TNSALP Pyridoxal-5'-phosphate Genotype-phenotype Asfotase alfa This research was funded by the Institute of Health Carlos III grants (PI18-00803 and PI18-01235), co-funded by the European Regional Development Fund (FEDER). In addition, JM.V-S and C.G-F are funded by predoctoral and postdoctoral fellowships, respectively, from the Institute of Health Carlos III (CM19/00188; CD20/00022). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. 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 ALPL 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 ALPL 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 ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL 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. 2021-06-01T06:47:15Z 2021-06-01T06:47:15Z 2021-04-21 info:eu-repo/semantics/article Villa-Suárez, J.M.; García-Fontana, C.; Andújar-Vera, F.; González-Salvatierra, S.; de Haro-Muñoz, T.; Contreras-Bolívar, V.; García-Fontana, B.; Muñoz-Torres, M. Hypophosphatasia: A Unique Disorder of Bone Mineralization. Int. J. Mol. Sci. 2021, 22, 4303. [https://doi.org/10.3390/ijms22094303] http://hdl.handle.net/10481/68947 10.3390/ijms22094303 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI