Safety and Efficacy of Treatment of Pediatric Cholesteryl Ester Storage Disease with Lovastatin

Abstract

ABSTRACT. The aim of this study was to prospectively assess the safety and efficacy of lovastatin in the treatment of cholesteryl ester storage disease in siblings who were ages 11.6 and 5 y at the beginning of treatment. Mean total and LDL cholesterol in the male proband, 7.40 and 5.68 mmol/L, respectively, on diet alone, fell 30% to 5.2 ( p 5 0.001) and 31% to 3.9 mmol/L ( p 5 0.001) on lovastatin 40 mg/d over 3.3 y, with simultaneous resolution of hepatosplenomegaly. In his sister, on lovastatin 20 mg/d for 1.5 y, total and LDL cholesterol fell, but not significantly; her hepatosplenomegaly was also reduced on treatment. Lovastatin was well tolerated without overt side effects or complications and without adverse changes in liver function tests or creatine phosphokinase. Normal and expected accretion of height and weight occurred during the treatment period for both children. Lovastatin appears to be a safe and effective treatment for pediatric cholesteryl ester storage disease. (Pediatr Res 32: 559-565, 1992) Abbreviations CESD, cholesteryl ester storage disease LDLC, low density lipoprotein cholesterol HDLC, high density lipoprotein cholesterol CPK, creatine phosphokinase GGT, 7-glutamyl transferase SGPT, serum glutamate pyruvate transaminase CESD is a rare, recessively inherited disorder characterized by very low or unmeasurable levels of the hepatic lysosomal enzyme cholesteryl ester hydrolase (1-14). Patients with CESD usually have hepatosplenomegaly because of hepatic lysosomal sequestration of cholesteryl ester and commonly have high plasma cholesterol, LDLC, and triglycerides and very low levels of HDLC. High LDLC and low HDLC in CESD patients puts them at markedly increased risk for premature coronary artery disease. Moreover, ongoing storage of cholesteryl esters in the hepatic lysosomes, augmented by hyperlipidemia, leads to progressive hepatosplenomegaly. Consequent complications may include hepatic fibrosis, cirrhosis, and liver failure, with associated portal hypertension, varices, and hypersplenism.Until the recent availability of lovastatin (1, 10, 1 l), CESD could not be satisfactorily treated because diet and other lipid lowering drugs were not effective. In 1987, successful therapy of CESD with the newly available hydroxymethylglutaryl-CoA reductase inhibitor, lovastatin, was reported by Ginsberg et al. (I).

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

“…Lovastatin and simvastatin have both been utilized in the clinic with varying rates of success. In some cases, statin therapy reduced hepatosplenomegaly and TG/CE levels in serum and in the liver [74, 95-97] while in other cases the reduction in TG/CE levels was not significant [98, 99]. The efficacy of statins is augmented when used in combination with other cholesterol lowering drugs, such as ezetimibe [100] and cholestyramine [101].…”

Cholesterol Ester Storage Disease (CESD) Diagnosed in an Asymptomatic Adult

“…The suppression of cholesterol synthesis and apolipoprotein B production by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (HMG CoA reductase inhibitors) can be considered as a useful therapeutic principle. Several authors have found beneficial results with lovastatin [16][17][18][19] and simvastatin [20], both alone and in association with cholestyramine [21], and ezetimibe [22] in reducing serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in young patients with CESD. However, the benefit of this therapy has been questioned by other authors [23].…”

Statins in children: What do we know and what do we need to do?

“…The addition of two studies in patients with NS only adds another 16 children. Children with unusual lipid abnormalities, such as Alagille's syndrome, cholesterol ester storage disease (CESD), and sitosterolemia, have also been prescribed statins, but the results are generally limited to individual patient responses that may be biased to the reporting of patients who responded rather than those who did not [27][28][29][30]. A similarly small number have been treated with very high doses of statins, with mixed results on neoplasms.…”