Hong_2022_Mol.Genet.Metab.Rep_33_100935

BACKGROUND: Lysosomal acid lipase deficiency (LAL-D) is a phenotypic continuum between the severe Wolman disease and the attenuated cholesteryl ester storage disease (CESD). OBJECTIVE: To study if the amount of residual LAL enzymatic activity in dried blood spots (DBS) correlates with the LAL-D disease severity. METHODS: DBS from Wolman and CESD patients, LAL-D carriers, and presumably unaffected random newborns were acquired. LAL enzymatic activity in DBS were measured using a novel, highly specific LAL substrate. RESULTS: Patients with Wolman disease displayed significantly lower LAL enzymatic activity compared to CESD patients. This was not observed with the traditional assay in which a non-specific substrate was used together with an LAL-specific inhibitor. CONCLUSION: The new LAL enzymatic activity assay using the specific substrate offers an improved biochemical genetics method for the diagnosis of LAL-D in symptomatic patients and more importantly, for the prognosis of asymptomatic patients who test positive in population-wide LAL-D newborn screening.