Lysosomal acid lipase (LAL) deficiency is a rare autosomal recessive disorder which causes two distinct clinical phenotypes: Wolman's disease and cholesterol ester storage disease.
Identification of rare diseases by screening a population selected on the basis of routine pathology results-the PATHFINDER project: lysosomal acid lipase/cholesteryl ester storage disease substudy.
Deficiency of LAL in humans leads to Wolman disease and cholesteryl ester storage disease that result, respectively, in the intralysosomal storage of both neutral lipids or only cholesteryl esters.
LAL-D presents as a clinical continuum with two phenotypes: the infantile-onset phenotype, formally referred to as Wolman disease, and the later-onset phenotype, formerly referred to as cholesteryl ester storage disease.
These findings, together with our previous observations when analyzing the mutations in WD and CESD patients lead to the conclusion that the more severe WD is due to mutations that absolutely abolish lysosomal acid lipase (LAL) enzyme activity and the cholesteryl ester storage disease phenotype is due to mutations that allow some residual LAL activity to be manifested.
A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.