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Lysosomal Acid Lipase Deficiency: Therapeutic Options

Authors Pastores GM, Hughes DA

Received 5 December 2019

Accepted for publication 16 January 2020

Published 11 February 2020 Volume 2020:14 Pages 591—601


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Tuo Deng

Gregory M Pastores,1 Derralynn A Hughes2

1Department of Medicine (Genetics)/National Centre for Inherited Metabolic Disorders, Mater Misericordiae University Hospital and University College Dublin, Dublin, Ireland; 2Royal Free London NHS Foundation Trust, University College London, London NW3 2QG, UK

Correspondence: Gregory M Pastores
National Centre for Inherited Metabolic Disorders, Mater Misericordiae University Hospital and University College Dublin, Dublin, Ireland
Tel +353 1 803 4878
Fax +353 1 803 4876

Abstract: 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.

Keywords: atherosclerosis, dyslipidemia, enzyme replacement therapy, hepatomegaly, lipid-lowering medications, lysosomal acid lipase deficiency, lysosomal storage disease

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