ABSTRACT
Wolman and colleagues [1] reported first one, then two more siblings in the same family, in whom the accumulation of cholesterol and triglycerides was associated with abdominal distension, hepatosplenomegaly and calcification of the adrenals. Death occurred within the first 3 months of life. The molecular defect in this disease is the lysosomal acid
lipase (EC 3.1.1.13) [2]. This lipase, first demonstrated to be defective in liver and spleen, is a 46 kDa glycoprotein active on both triglycerides and cholesteryl esters (Figure 98.1). This enzyme is also defective in cholesteryl ester storage disease. The two diseases are allelic, caused by mutations at the LIPA locus on chromosome 10q23.2-q23.3 [3]. In general the mutations in patients with Wolman disease are major alterations that lead to absence of enzyme activity [4-6]. Most patients with cholesteryl ester storage disease have at least one copy of a single mutant allele, a G934A mutation at the exon 8 splice junction, which leads to exon skipping and the loss of codons 254-277 [7,8].
