Cholesteryl ester storage disease: Pathologic changes in an affected fetus

Abstract

The prenatal diagnosis of cholesteryl ester storage disease, a rare autosomal recessive disorder, was made by demonstration of deficient lysosomal acid lipase activity in cultured amniocytes from an at-risk fetus. The histochemical and ultrastructural changes in the affected fetus (at 17 gestational weeks) are described and compared to findings in liver and duodenal biopsy specimens from a 9-year-old homozygous female. Massive lysosomal cholesterol and lipid accumulation was demonstrated in fetal hepatocytes, adrenal cells and syncytiotrophoblasts. Of particular note was the observation of extensive necrosis in the fetal adrenal glands. Necrosis of the adrenals may precede the calcification observed in some patients with cholesteryl ester storage disease and in most patients with Wolman disease, an allelic variant due to lysosomal acid lipase deficiency. Fibrosis of the liver and lipid accumulation in macrophages in liver and duodenum, which were present in the 9-year-old homozygote, were not observed in the affected fetus, and therefore, may represent later manifestations of the disease.

Loss of lysosomal protein NCU-G1 results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells

“…These vary from neurological and developmental problems to internal organ injury (Jevon and Dimmick, 1998; Futerman and van Meer, 2004; Parkinson-Lawrence et al, 2010). Liver fibrosis is a common finding in several lysosomal storage diseases, including Gaucher disease (James et al, 1981; Lachmann et al, 2000), cholesteryl ester storage disease (Desai et al, 1987; Bernstein et al, 2013), and Niemann Pick A/B and C disease (Kelly et al, 1993; Takahashi et al, 1997). Recent work by Moles et al demonstrated a direct link between lysosomal dysfunction and liver fibrogenesis through the lysosomal enzyme acidic sphingomyelinase, deficient in Niemann Pick type A/B (Takahashi et al, 1997).…”

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

“…Because 4-MU palmitate cleavage is not specific to LAL, a specific inhibitor is used to differentiate between general lipase activity and LAL activity. This assay can also be performed in amniotic fluid cells for prenatal screening [44, 45]. While assaying for LAL activity may give a clear diagnosis of LAL deficiency, a definitive diagnosis may be made by the exonic sequencing of the LIPA gene.…”

Isolated fetal ascites caused by Wolman disease

“…X‐ray films, computed tomography scans and ultrasound scans can detect adrenal calcifications, hepatosplenomegaly or bowel wall thickening5–7. Desai et al 8 described the histopathological findings in a fetus with CESD, following termination of pregnancy at 17 gestational weeks. However, they did not include any gross morphological or ultrasound data.…”