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Hypophosphatasia
Hypophosphatasia (HPP) is an inherited metabolic disease caused by loss-of-function mutations in the tissue non-specific alkaline phosphatase (TNAP) gene. Reduced activity of TNAP leads to the accumulation of its substrates, mainly inorganic pyrophosphate and pyridoxal-5′-phosphate, metabolic aberra...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658462/ https://www.ncbi.nlm.nih.gov/pubmed/34884378 http://dx.doi.org/10.3390/jcm10235676 |
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author | Tournis, Symeon Yavropoulou, Maria P. Polyzos, Stergios A. Doulgeraki, Artemis |
author_facet | Tournis, Symeon Yavropoulou, Maria P. Polyzos, Stergios A. Doulgeraki, Artemis |
author_sort | Tournis, Symeon |
collection | PubMed |
description | Hypophosphatasia (HPP) is an inherited metabolic disease caused by loss-of-function mutations in the tissue non-specific alkaline phosphatase (TNAP) gene. Reduced activity of TNAP leads to the accumulation of its substrates, mainly inorganic pyrophosphate and pyridoxal-5′-phosphate, metabolic aberrations that largely explain the musculoskeletal and systemic features of the disease. More than 400 ALPL mutations, mostly missense, are reported to date, transmitted by either autosomal dominant or recessive mode. Severe disease is rare, with incidence ranging from 1:100,000 to 1:300,000 live births, while the estimated prevalence of the less severe adult form is estimated to be between 1:3100 to 1:508, in different countries in Europe. Presentation largely varies, ranging from death in utero to asymptomatic adults. In infants and children, clinical features include skeletal, respiratory and neurologic complications, while recurrent, poorly healing fractures, muscle weakness and arthropathy are common in adults. Persistently low serum alkaline phosphatase is the cardinal biochemical feature of the disease. Management requires a dedicated multidisciplinary team. In mild cases, treatment is usually symptomatic. Severe cases, with life-threating or debilitating complications, can be successfully treated with enzyme replacement therapy with asfotase alfa. |
format | Online Article Text |
id | pubmed-8658462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86584622021-12-10 Hypophosphatasia Tournis, Symeon Yavropoulou, Maria P. Polyzos, Stergios A. Doulgeraki, Artemis J Clin Med Review Hypophosphatasia (HPP) is an inherited metabolic disease caused by loss-of-function mutations in the tissue non-specific alkaline phosphatase (TNAP) gene. Reduced activity of TNAP leads to the accumulation of its substrates, mainly inorganic pyrophosphate and pyridoxal-5′-phosphate, metabolic aberrations that largely explain the musculoskeletal and systemic features of the disease. More than 400 ALPL mutations, mostly missense, are reported to date, transmitted by either autosomal dominant or recessive mode. Severe disease is rare, with incidence ranging from 1:100,000 to 1:300,000 live births, while the estimated prevalence of the less severe adult form is estimated to be between 1:3100 to 1:508, in different countries in Europe. Presentation largely varies, ranging from death in utero to asymptomatic adults. In infants and children, clinical features include skeletal, respiratory and neurologic complications, while recurrent, poorly healing fractures, muscle weakness and arthropathy are common in adults. Persistently low serum alkaline phosphatase is the cardinal biochemical feature of the disease. Management requires a dedicated multidisciplinary team. In mild cases, treatment is usually symptomatic. Severe cases, with life-threating or debilitating complications, can be successfully treated with enzyme replacement therapy with asfotase alfa. MDPI 2021-12-01 /pmc/articles/PMC8658462/ /pubmed/34884378 http://dx.doi.org/10.3390/jcm10235676 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Tournis, Symeon Yavropoulou, Maria P. Polyzos, Stergios A. Doulgeraki, Artemis Hypophosphatasia |
title | Hypophosphatasia |
title_full | Hypophosphatasia |
title_fullStr | Hypophosphatasia |
title_full_unstemmed | Hypophosphatasia |
title_short | Hypophosphatasia |
title_sort | hypophosphatasia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658462/ https://www.ncbi.nlm.nih.gov/pubmed/34884378 http://dx.doi.org/10.3390/jcm10235676 |
work_keys_str_mv | AT tournissymeon hypophosphatasia AT yavropouloumariap hypophosphatasia AT polyzosstergiosa hypophosphatasia AT doulgerakiartemis hypophosphatasia |