SITOSTEROLEMIA - OPPOSING EFFECTS OF CHOLESTYRAMINE AND LOVASTATIN ONPLASMA STEROL LEVELS IN A HOMOZYGOUS GIRL AND HER HETEROZYGOUS FATHER

Sitosterolemia is a genetic disorder characterized by sitosterol accum ulation in plasma and clinically accelerated atherosclerosis. Under a condition of metabolic control with a 30% fat, low-sitosterol diet, we compared the effects of monotherapy and dual-drug treatment with lova statin and cholestyramine on plasma sterol parameters and endogenous c holesterol synthesis in a homozygous sitosterolemic patient with conco mitant heterozygous familial hypercholesterolemia (FH), her obligate h eterozygous father, and hyperlipidemic control subjects. We found that for both the sitosterolemic homozygote and heterozygote, cholestyrami ne plus lovastatin dual therapy proved not to be superior to either dr ug treatment alone. In the homozygous patient, cholestyramine accounte d for the decrease of plasma sterol (ie, lovastatin was ineffective), whereas in the heterozygote, lovastatin represented the margin of diff erence (ie, low dose cholestyramine was relatively ineffective). Thus, the best treatment option for this homozygote child and her heterozyg ote father appears to be monotherapy with cholestyramine and lovastati n, respectively. Stimulation by bile acid malabsorption produced a dra matic decrease of plasma sterols in the homozygote, without increasing endogenous cholesterol synthesis, but this therapy was ineffective in the heterozygote. Decreasing endogenous cholesterol synthesis with lo vastatin was effective in the heterozygote, but ineffective in the hom ozygote. In suspected sitosterolemia, a poor sterol response to lovast atin and a dramatic response to cholestyramine may differentiate homoz ygous from heterozygous and other familiar forms of hyperlipidemia. Co pyright (C) 1996 by W.B. Saunders Company.