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Lysosomal Acid Lipase Deficiency: Therapeutic Options

Lysosomal acid lipase (LAL) deficiency is a metabolic (storage) disorder, encompassing a severe (Wolman disease) and attenuated (Cholesterol ester storage disease) subtype; both inherited as autosomal recessive traits. Cardinal clinical features include the combination of hepatic dysfunction and dys...

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Autores principales: Pastores, Gregory M, Hughes, Derralynn A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023879/
https://www.ncbi.nlm.nih.gov/pubmed/32103901
http://dx.doi.org/10.2147/DDDT.S149264
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author Pastores, Gregory M
Hughes, Derralynn A
author_facet Pastores, Gregory M
Hughes, Derralynn A
author_sort Pastores, Gregory M
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description Lysosomal acid lipase (LAL) deficiency is a metabolic (storage) disorder, encompassing a severe (Wolman disease) and attenuated (Cholesterol ester storage disease) subtype; both inherited as autosomal recessive traits. Cardinal clinical features include the combination of hepatic dysfunction and dyslipidemia, as a consequence of cholesteryl esters and triglyceride accumulation, predominately in the liver and vascular and reticuloendothelial system. Significant morbidity can arise, due to liver failure and/or atherosclerosis; in part related to the severity of the underlying gene defect and corresponding enzyme deficiency. Diagnosis is based on demonstration of decreased LAL enzyme activity, complemented by analysis of the cognate gene defects. Therapeutic options include dietary manipulation and the use of lipid-lowering drugs. Sebelipase alfa, a recombinant enzyme replacement therapy, has garnered regulatory approval, following demonstration of improvements in disease-relevant markers and clinical benefit in clinical trials, which included increased survival in the most severe cases.
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spelling pubmed-70238792020-02-26 Lysosomal Acid Lipase Deficiency: Therapeutic Options Pastores, Gregory M Hughes, Derralynn A Drug Des Devel Ther Review Lysosomal acid lipase (LAL) deficiency is a metabolic (storage) disorder, encompassing a severe (Wolman disease) and attenuated (Cholesterol ester storage disease) subtype; both inherited as autosomal recessive traits. Cardinal clinical features include the combination of hepatic dysfunction and dyslipidemia, as a consequence of cholesteryl esters and triglyceride accumulation, predominately in the liver and vascular and reticuloendothelial system. Significant morbidity can arise, due to liver failure and/or atherosclerosis; in part related to the severity of the underlying gene defect and corresponding enzyme deficiency. Diagnosis is based on demonstration of decreased LAL enzyme activity, complemented by analysis of the cognate gene defects. Therapeutic options include dietary manipulation and the use of lipid-lowering drugs. Sebelipase alfa, a recombinant enzyme replacement therapy, has garnered regulatory approval, following demonstration of improvements in disease-relevant markers and clinical benefit in clinical trials, which included increased survival in the most severe cases. Dove 2020-02-11 /pmc/articles/PMC7023879/ /pubmed/32103901 http://dx.doi.org/10.2147/DDDT.S149264 Text en © 2020 Pastores and Hughes. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Review
Pastores, Gregory M
Hughes, Derralynn A
Lysosomal Acid Lipase Deficiency: Therapeutic Options
title Lysosomal Acid Lipase Deficiency: Therapeutic Options
title_full Lysosomal Acid Lipase Deficiency: Therapeutic Options
title_fullStr Lysosomal Acid Lipase Deficiency: Therapeutic Options
title_full_unstemmed Lysosomal Acid Lipase Deficiency: Therapeutic Options
title_short Lysosomal Acid Lipase Deficiency: Therapeutic Options
title_sort lysosomal acid lipase deficiency: therapeutic options
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023879/
https://www.ncbi.nlm.nih.gov/pubmed/32103901
http://dx.doi.org/10.2147/DDDT.S149264
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