Recommendations for overcoming challenges in the diagnosis of lysosomal acid lipase deficiency

ABSTRACT

Introduction

Lysosomal acid lipase deficiency disease (LALD; MIM#278000) is an ultrarare lysosomal storage disease with a wide range of phenotypic variability. It is caused by the deficient activity of lysosomal acid lipase (LAL) enzyme, encoded by LIPA. Consequently, it leads to the buildup of cholesterol esters and triglycerides within the lysosomes, in the liver, spleen, adrenal glands, intestinal wall, and vascular tree. Early diagnosis is important to avoid progressive impaired liver function and an elevated risk of cardiovascular complications.

Areas covered

A systematic review has been carried out in accordance with the Preferred Reporting Items for Systematic Review and Meta Analyses (PRISMA) guidelines. All original articles and review articles published up to December 2021 about the diagnosis and follow-up of lysosomal acid lipase deficiency, Wolman disease, acid cholesterol ester hydrolase deficiency, and cholesterol ester hydrolase deficiency storage disease were reviewed by three independent researchers. A total of 169 articles were included.

Expert opinion

The identification of LALD by activity determination techniques using a dry blood spot has facilitated rapid and accurate diagnosis in screening programs. It is important to reduce the mortality associated with severe phenotypes and morbi-mortality in mild phenotypes, since safe and effective enzyme replacement therapy is available.

KEYWORDS:

• Acid lipase lysosomal deficiency
• diagnosis
• enzymatic procedure
• genetic analysis
• consequences diagnostic delay

Article highlights

• Lysosomal acid lipase deficiency, Wolman disease, acid cholesterol ester hydrolase deficiency, and cholesterol ester hydrolase deficiency storage disease are terms for the same disease, which is caused by a deficient activity of the enzyme lysosomal acid lipase, secondary to variants in the LIPA gene.

• The diagnosis of lysosomal acid lipase deficiency may be missed in adults and juveniles.

• It is necessary to consider the diagnosis of lysosomal acid lipase deficiency in hyperlipidemia and chronic liver dysfunction of non-identified origin.

• Enzymatic determinations in dried blood spots and genetic panels including the E8SJM variant allow the identification of most cases.

• The importance of early diagnosis is justified by the availability of effective enzyme replacement therapy to prevent devastating complications.

Acknowledgments

The authors acknowledge the Asociación Española Deficit de Lipasa Acida Lisosomal (AELALD) for their invaluable collaboration.

Declaration of interest

J J Cebolla is an employee of Takeda Pharmaceuticals, outside of the submitted work, without stock options. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was supported by a research grant for the FEETEG.