TY - JOUR
T1 - PRENATAL DIAGNOSIS OF HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLÆMIA. Expression of a Genetic Receptor Disease in Utero
AU - Brown, MichaelS
AU - Goldstein, JosephL
AU - Vandenberghe, Kamiel
AU - Fryns, JeanPierre
AU - Kovanen, PetriT
AU - Eeckels, Roger
AU - Van Den Berghe, Herman
AU - Cassiman, JeanJacques
N1 - Funding Information:
This survey was partly supported by the Fukuoka Chest Disease Council. I thank Dr Noburu Ishinishi, Professor of Hygiene at Kyushu
PY - 1978/3/11
Y1 - 1978/3/11
N2 - Cultured amniotic-fluid cells from a fetus at risk for homozygous familial hypercholesterolæmia (F.H.) almost completely lacked cell-surface receptors for plasma low-density lipoprotein (L.D.L.), as evidenced by direct measurement of binding, uptake, and degradation of 125I-L.D.L. Functional consequences of L.D.L. binding to the receptor-i.e., suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and stimulation of cholesterol esterification-were proportionately reduced when compared with results in cultured amniotic cells from two control fetuses. On the basis of these findings, homozygous F.H. was diagnosed and the pregnancy was terminated at the 20th week. The diagnosis of homozygous F.H. was confirmed by a serum-cholesterol of the aborted fetus of 279 mg/dl, a value 9 times the mean of four control fetuses of similar gestational age. More than 80% of the serum-cholesterol of the affected fetus was contained within L.D.L. Prenatal diagnosis of homozygous F.H. now seems practical; moreover, the finding of a raised serum-L.D.L. in the affected fetus indicates that the L.D.L. receptor is normally functional as early as the 20th week of fetal life.
AB - Cultured amniotic-fluid cells from a fetus at risk for homozygous familial hypercholesterolæmia (F.H.) almost completely lacked cell-surface receptors for plasma low-density lipoprotein (L.D.L.), as evidenced by direct measurement of binding, uptake, and degradation of 125I-L.D.L. Functional consequences of L.D.L. binding to the receptor-i.e., suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and stimulation of cholesterol esterification-were proportionately reduced when compared with results in cultured amniotic cells from two control fetuses. On the basis of these findings, homozygous F.H. was diagnosed and the pregnancy was terminated at the 20th week. The diagnosis of homozygous F.H. was confirmed by a serum-cholesterol of the aborted fetus of 279 mg/dl, a value 9 times the mean of four control fetuses of similar gestational age. More than 80% of the serum-cholesterol of the affected fetus was contained within L.D.L. Prenatal diagnosis of homozygous F.H. now seems practical; moreover, the finding of a raised serum-L.D.L. in the affected fetus indicates that the L.D.L. receptor is normally functional as early as the 20th week of fetal life.
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U2 - 10.1016/S0140-6736(78)90552-4
DO - 10.1016/S0140-6736(78)90552-4
M3 - Article
C2 - 76071
AN - SCOPUS:0017798814
SN - 0140-6736
VL - 311
SP - 526
EP - 529
JO - The Lancet
JF - The Lancet
IS - 8063
ER -