Villa-Suárez, Juan MiguelGarcía-Fontana, CristinaAndújar-Vera, FranciscoGonzález-Salvatierra, Sheilade Haro-Muñoz, TomásContreras-Bolívar, VictoriaGarcía-Fontana, BeatrizMuñoz-Torres, Manuel2022-04-052022-04-052021-04-21Villa-Suárez JM, García-Fontana C, Andújar-Vera F, González-Salvatierra S, de Haro-Muñoz T, Contreras-Bolívar V, et al. Hypophosphatasia: A Unique Disorder of Bone Mineralization. Int J Mol Sci. 2021 Apr 21;22(9):4303http://hdl.handle.net/10668/3519Hypophosphatasia (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-50-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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/HypophosphatasiaTNSALPPyridoxal-5′-phosphateGenotype-phenotypeAsfotase alfaHipofosfatasiaFosfato de piridoxalFosfatasa alcalinaTerapia de reemplazo enzimáticoMutaciónMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Alkaline PhosphataseMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Alkaline PhosphataseMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Enzyme Therapy::Enzyme Replacement TherapyMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Metal Metabolism, Inborn Errors::HypophosphatasiaMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutationreview article33919113open access10.3390/ijms220943031422-0067PMC8122659