Stratification of Patients with Lysosomal Acid Lipase Deficiency by Enzyme Activity in Dried Blood Spots

Lysosomal acid lipase deficiency (LAL-D) is a phenotypic continuum between the severe Wolman disease and the attenuated cholesteryl ester storage disease (CESD).To study if the amount of residual LAL enzymatic activity in dried blood spots (DBS) correlates with the LAL-D disease severity.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.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.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.