Subclinical course of cholesteryl ester storage disease in an adult with hypercholesterolemia, accelerated atherosclerosis, and liver cancer

Few eases of asymptomatic cholesteryl ester storage disease (CESD) due to l ow enzymatic activity of human lysosomal acid lipase/cholesteryl ester hydr olase (hLAL) have been reported thus far in adults. Here, we describe a 51- year-old man with a long clinical history of mixed hyperlipoproteinemia and severe premature atherosclerosis, but with no signs of hepatomegaly, liver dysfunction, or splenomegaly, The disease was discovered by chance in a bi opsy performed because of suspected liver cancer (proven to be a cholangioc arcinoma), Residual hLAL activity in peripheral leukocytes was determined t o be 6% of control values. DNA sequence and restriction fragment length pol ymorphism analysis demonstrated that the patient was a compound heterozygot e for the prevalent CESD exon 8 splice site mutation (G934A) and the deleti on of a C (nucleotide 673, 674, or 675) in exon 6 of the hLAL gene, resulti ng in premature termination of protein translation at residue 195. The pati ent died of liver failure as a consequence of extensive tumor infiltration at age 52, Lipid analysis revealed moderate cholesteryl ester storage in th e liver and in the suprarenal cortex, and massive accumulation in the testi cular histiocytes and Leydig cells, resulting in a pronounced secondary atr ophy of the seminiferous tubules, Our ease study demonstrates that hepatome galy is an inconstant feature, even in CESD patients compound heterozygous for a Wolman mutation which results in complete loss of hLAL enzymic activi ty It also highlights the need to be aware of this condition as it may be u nderdiagnosed.