The liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay can identify patients with lysosomal acid lipase deficiency (LAL-D), according to the results of a new study published in Molecular Genetics and Metabolism Reports.

Due to the robustness of the technique, it can be used and should be implemented for newborn screening, the authors of the study say. 

LAL-D can be diagnosed using dried blood spots. However, because there are many lipases present in dried blood spots, lalistat-2, which is a lysosomal acid lipase (LAL)-specific inhibitor, is usually used. Recently, a novel substrate that is LAL-specific has been reported.

Continue Reading

Here, a team of researchers from the United Kingdom and Japan assessed the LAL enzyme activity of a Japanese population with the LAL-specific substrate using an LC-MS/MS-based assay to test whether individuals affected by LAL-D could be identified this way.

Read more about the diagnosis of LAL-D

The researchers first performed an assay validation and then used the assay to analyze the activity of the LAL enzyme in a control Japanese population and in individuals affected by Wolman disease and cholesteryl ester storage disorder (CESD), the 2 types of LAL-D.

The results showed that the average enzyme activity for control newborns was between 70 and 177.8 μmol/h/L, while the average enzyme activities in patients with Wolman disease and CESD were 5.7 to 7.5 μmol/h/L and 4.5 to 5.1 μmol/h/L, respectively. 

“These results suggest that an LAL-D-affected individual can be readily identified by enzyme activity using LC-MS/MS-based technique,” the researchers concluded. 

LAL-D is a rare genetic disease that can be life-threatening. Early diagnosis is very important, as it determines the right treatment course.


Ohira M, Barr M, Okuyama T, Mashima R. LC-MS/MS-based enzyme assay for lysosomal acid lipase using dried blood spots. Mol Genet Metab Rep. Published online August 26, 2022. doi:10.1016/j.ymgmr.2022.100913