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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...

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Autores principales: Tournis, Symeon, Yavropoulou, Maria P., Polyzos, Stergios A., Doulgeraki, Artemis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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
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