Lovastatin therapy for cholesterol ester storage disease in two sisters

Tarantino, Michael D.; McNamara, Donald J.; Granstrom, Per; Ellefson, Ralph D.; Unger, Evan C.; Udall, John N.

doi:10.1016/s0022-3476(05)81866-9

Cited by 48 publications

(19 citation statements)

References 21 publications

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“…To the extent that lovastatin reduces endogenous cholesterol biosynthesis (I), because most of the cholesteryl ester in the hepatic lysosomes comes from cholesterol esterified in the blood, lovastatin should reduce the amount of cholesteryl ester returning to the liver and should also reduce LDLC levels. Our findings over treatment periods of 3.3 and 1.5 y are congruent with those of Tarantino et al (10). In two sisters with CESD (ages 4 and 17 y), Tarantino et al gave lovastatin 20 mg for 6 mo and reported marked decreases in plasma cholesterol, triglyceride, and LDLC, with increases in HDLC.…”

Section: Discussionsupporting

confidence: 91%

“…A concomitant hyperlipidemia, inherited separately, might explain some of the differences in lipid levels in patients with CESD. As noted by Tarantino et al (10) " . .…”

Section: Discussionmentioning

confidence: 79%

“…There was a decrease in LDLC and an increase in HDLC attributed to lovastatin therapy; liver and spleen size were reduced during therapy, as judged by physical examination. In contrast to the successful treatment of pediatric CESD reported by Tarantino et al (10) and McCoy and Yokoyama (1 l), DiBisceglie et al (12) treated three children with CESD with lovastatin 40 mg/d for at least 12 mo and observed no significant changes in serum lipoprotein concentrations or liver histopathology after therapy. It is not clear why lovastatin was effective in our current study, although more so in the proband than his sister, and in those of Tarantino et al (10) and McCoy et al (1 1) but not in the report of Di-Bisceglie et al (12).…”

Section: Discussionmentioning

confidence: 85%

“…. lovastatin may be effective in treating children with cholesterol-ester storage disease" (10). McCoy and Yokoyama (1 1) recently reported treatment of a 13-y-old boy with CESD with combined cholestyramine and lovastatin over a period of 1.5 y.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1992

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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).

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Section: Discussionsupporting

confidence: 91%

“…A concomitant hyperlipidemia, inherited separately, might explain some of the differences in lipid levels in patients with CESD. As noted by Tarantino et al (10) " . .…”

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 1992

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“…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].…”

Section: Discussionmentioning

confidence: 99%