The turnover of 125I-labeled low density lipoprotein (LDL) and the total body balance of cholestrol were studied in a 6-yr-old girl with the homozygous form of familial hypercholesterolemia (FH) before and after the surgical creation of an end-to-side portacaval shunt. The results were compared with those of similar studies simultaneously performed in untreated patients with the heterozygous form of FH and with the results of earlier studies performed on normolipidemic subjects. Before shunt surgery, the rate of synthesis of LDL in the FH homozygote (mg/kg per day) was fourfold higher than in normolipidemic subjects and twofold higher than in her heterozygous mother. The fractional catabolic rate for LDL in the homozygote was decreased to 33% of normal control values. The rate of cholesterol synthesis, estimated by chemical sterol balance, was higher in the FH homozygote than in two FH heterozygotes of similar age studied simultaneously. When considered in relation to the markedly elevated level of plasma cholesterol, the observed rate of cholesterol synthesis in the FH homozygote was inappropriately elevated. Bile acid production was normal in all three children. 5 mo after shunt surgery, the rate of LDL synthesis in the homozygote had declined by 48% as compared with the preoperative value, and this caused a 39% drop in the plasma LDL cholesterol level despite a 17% reduction in the fractional catabolic rate of the lipoprotein. The rate of cholesterol synthesis fell by 62% as compared with the preoperative value. The findings of an inappropriately elevated rate of production of both cholesterol and LDL as well as a reduced fractional catabolic rate for the lipoprotein in the untreated FH homozygote are consistent with results of studies in cultured fibroblasts indicating that the primary genetic defect in FH involves a deficiency in a cell-surface receptor for LDL that regulates both cholesterol synthesis and LDL degradation. Although the mechanism for the decline in production of cholesterol and LDL after portacaval shunt surgery is unknown, it was observed that these changes were associated with marked increases in the plasma concentrations of bile acids and glucagon.
D W Bilheimer, J L Goldstein, S M Grundy, M S Brown
Guidelines: The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. We reserve the right to edit any letter for length, content, and clarity. Authors will be notified by e-mail if their letters were accepted. No appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editors directly at email@example.com.