{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:12:54Z","timestamp":1793643174763,"version":"4.5.1"},"reference-count":122,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute of Health Carlos III","award":["PI18-00803"],"award-info":[{"award-number":["PI18-00803"]}]},{"name":"Institute of Health Carlos III","award":["PI18-01235"],"award-info":[{"award-number":["PI18-01235"]}]},{"name":"Institute of Health Carlos III","award":["CM19\/00188"],"award-info":[{"award-number":["CM19\/00188"]}]},{"name":"Institute of Health Carlos III","award":["CD20\/00022"],"award-info":[{"award-number":["CD20\/00022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2032-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.<\/jats:p>","DOI":"10.3390\/ijms22094303","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T12:47:07Z","timestamp":1619009227000},"page":"4303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Hypophosphatasia: A Unique Disorder of Bone Mineralization"],"prefix":"10.3390","volume":"22","author":[{"given":"Juan Miguel","family":"Villa-Su\u00e1rez","sequence":"first","affiliation":[{"name":"Clinical Analysis Unit, University Hospital Cl\u00ednico San Cecilio, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9328-6022","authenticated-orcid":false,"given":"Cristina","family":"Garc\u00eda-Fontana","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"},{"name":"Endocrinology and Nutrition Unit, University Hospital Cl\u00ednico San Cecilio, 18016 Granada, Spain"},{"name":"CIBERFES, Institute of Health Carlos III, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2663-8809","authenticated-orcid":false,"given":"Francisco","family":"And\u00fajar-Vera","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Gonz\u00e1lez-Salvatierra","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"},{"name":"Endocrinology and Nutrition Unit, University Hospital Cl\u00ednico San Cecilio, 18016 Granada, Spain"},{"name":"Department of Medicine, University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"de Haro-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Clinical Analysis Unit, University Hospital Cl\u00ednico San Cecilio, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Contreras-Bol\u00edvar","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"},{"name":"Endocrinology and Nutrition Unit, University Hospital Cl\u00ednico San Cecilio, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4134-5561","authenticated-orcid":false,"given":"Beatriz","family":"Garc\u00eda-Fontana","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"},{"name":"Endocrinology and Nutrition Unit, University Hospital Cl\u00ednico San Cecilio, 18016 Granada, Spain"},{"name":"CIBERFES, Institute of Health Carlos III, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9645-3260","authenticated-orcid":false,"given":"Manuel","family":"Mu\u00f1oz-Torres","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"},{"name":"Endocrinology and Nutrition Unit, University Hospital Cl\u00ednico San Cecilio, 18016 Granada, Spain"},{"name":"CIBERFES, Institute of Health Carlos III, 18012 Granada, Spain"},{"name":"Department of Medicine, University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1750-1172-2-40","article-title":"Hypophosphatasia","volume":"2","author":"Mornet","year":"2007","journal-title":"Orphanet J. 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