Diagnosis of familial hypercholesterolemia by measurement of sterol synthesis in cultured skin fibroblasts.

The incorporation of radioactive acetate into the digitonin precipitable fraction (cholesterol) was measured in monolayers of primary cultures of skin fibroblasts. Mean incorporation was increased approximately 20-fold in 4 subjects homozygous for familial hypercholesterolemia (FH) and 4-fold in 6 heterozygotes derived from the immediate family of homozygotes. Incorporation was normal in 4 subjects with Type IV and V hyperlipoproteinemia. In cells that had been preincubated in lipid free medium, incorporation by cells from homozygotes was equal to controls, denoting a derangement in the feedback inhibition of cholesterol synthesis by medium lipids in paralleled the values obtained for sterol synthesis. The assay described could be useful in making an "etiologic" diagnosis of familial hypercholesterolemia and could possible identify variants of monogenic hyperbetalipoproteinemia.