Lukacs_2017_Clin.Chim.Acta_471_201

Lysosomal acid lipase deficiency (LAL-D) is an inherited, autosomal recessive lysosomal storage disorder characterized by progressive damage in multiple organ systems. Diagnosis is especially important in infants, in whom the course of disease is rapidly lethal without treatment. The recent regulatory approval of recombinant human lysosomal acid lipase (LAL), sebelipase alfa, merits rapid diagnosis in clinical routine, particularly in infants. A method for measuring LAL activity in dried blood spot (DBS) samples using the highly specific LAL inhibitor Lalistat 2 is available. This method is shown to effectively discriminate between individuals with LAL-D and unaffected controls. With the increase in DBS LAL testing since the original publication of this method, a need to optimise assay performance has been identified. Here, we describe refinements to the DBS assay, including technical modifications, quality control measures and best-practice guidance for interpreting and reporting results. Particular attention is paid to alternatives to the use of mercuric chloride as the stop reagent and the choice of excitation wavelength for 4-methylumbelliferone palmitate under assay conditions at pH4.0. In addition, a simpler method of reporting results is proposed using cutoffs based on percentage mean normal enzyme activity.