Researchers discovered that identifying lysosomal acid lipase deficiency (LAL-D) via activity determination techniques using a dried blood spot can accurately diagnose the disease and allow for treatment initiation, according to a study published in Expert Opinions on Orphan Drugs. 

“LAL-D . . . is an ultra-rare lysosomal storage disease with a wide range of phenotypic variability and age of onset,” the authors of the study wrote. “Early diagnosis is important to avoid progressive impaired liver function and an elevated risk of cardiovascular complications.”

The authors conducted a literature review up to December 2021 of all available studies regarding the diagnosis and follow-up of LAL-D cases, including its subtypes, Wolman disease and cholesteryl ester storage disease. They identified 169 articles that fit their research criteria.

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The researchers reported that evaluating LAL activity, followed by LIPA sequencing, is one of the quickest ways to obtain an accurate diagnosis. Hence, screening programs using a dried blood spot test can accurately identify individuals with the disease, even if they have a milder phenotype. 

Read more about LAL-D etiology 

Although the statistical yield for conducting LAL-D testing may seem low, future technology can make screening programs even more efficient. 

“As a vision for the future, with the implementation of . . . analysis with ‘big data’ and ‘machine learning’ procedures, and the possibility of data integration and the continuous reduction of costs, we hope to obtain tools that will facilitate the identification and management of diseases with low prevalence that are involved in multiple functions and organs in the body,” the authors of the study wrote. 

Because of its scarcity, the disease is poorly understood; this is due in part to past difficulties in diagnosing it. It was first described in the 1950s, but only a limited number of case series have been collected. 

Today, the advent of enzyme replacement therapy has drastically changed the prognosis of patients with LAL-D who are on treatment. The onus is therefore on physicians to diagnose this condition early to avoid liver and cardiovascular complications. 


Giraldo P, López de Frutos L, Cebolla JJ. Recommendations for overcoming challenges in the diagnosis of lysosomal acid lipase deficiency. Expert Opin Orphan Drugs. Published online October 1, 2022. doi:10.1080/21678707.2022.2131393