Abstract
BackgroundCholesterol ester storage disease (CESD) is an autosomal recessive illness that results from mutations in the LIPA gene encoding lysosomal acid lipase. CESD patients present in childhood with hepatomegaly and dyslipidemia characterized by elevated total and low-density lipoprotein cholesterol (LDL-C), with elevated triglycerides and depressed high-density lipoprotein cholesterol (HDL-C). Usual treatment includes a low fat diet and a statin drug.ResultsIn an 18-year old with CESD, we documented compound heterozygosity for two LIPA mutations: a novel frameshift nonsense mutation and a deletion of exon 8. The patient had been treated with escalating doses of lovastatin for ~80 months, with ~15% decline in mean LDL-C. The addition of ezetimibe 10 mg to lovastatin 40 mg resulted in an additional ~16% decline in mean LDL-C.ConclusionThese preliminary anecdotal findings in a CESD patient with novel LIPA mutations support the longer term safety of statins in an adolescent patient and provide new data about the potential efficacy and tolerability of ezetimibe in this patient group.
Highlights
Cholesterol ester storage disease (CESD) is an autosomal recessive illness that results from mutations in the LIPA gene encoding lysosomal acid lipase
Cholesteryl ester storage disease (CESD; MIM 278000) is an autosomal recessive disorder caused by a deficiency of lysosomal acid lipase (LAL; acid cholesteryl hydrolase; EC 3.1.1.13)
LAL is responsible for the intralysosomal hydrolysis of cholesteryl esters (CE) and triglycerides (TG) [1]
Summary
Cholesterol ester storage disease (CESD) is an autosomal recessive illness that results from mutations in the LIPA gene encoding lysosomal acid lipase. CESD patients present in childhood with hepatomegaly and dyslipidemia characterized by elevated total and low-density lipoprotein cholesterol (LDL-C), with elevated triglycerides and depressed high-density lipoprotein cholesterol (HDL-C). Cholesteryl ester storage disease (CESD; MIM 278000) is an autosomal recessive disorder caused by a deficiency of lysosomal acid lipase (LAL; acid cholesteryl hydrolase; EC 3.1.1.13). Patients with CESD present in childhood with hepatomegaly, hypercholesterolemia and hypertriglyceridemia; most are diagnosed by age 20 [1]. Wolman disease (WD; MIM 278000) results from mutations in LIPA. WD is characterized by early death (usually before age 6 months) and widespread intracellular storage of both CE and TG, mainly in liver, adrenal glands and intestine [1]. In vitro catalytic activity was decreased ~200-fold in WD fibroblasts, but only ~50-fold in CESD fibroblasts [5], showing correlation with the differences in phenotypic severity [6,7]
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