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.
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.
Previous studies have indicated that compound heterozygosity consisting of a G-->A mutation at the 3'-splice junction of exon 8 (E8SJM-allele) together with a null allele of the gene encoding lysosomal acid lipase leads to cholesterol ester storage disease.
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.
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.