Cholesterol metabolism in normal and heterozygous familial hypercholesterolemic newborns.

In heterozygous familial hypercholesterolemia (FH), serum low-density lipoprotein (LDL) cholesterol levels are frequently increased in utero. A unique Finnish FH population, FH-North Karelia (FH-NK), has been identified, providing an excellent opportunity to study the diagnostic significance of cholesterol metabolism in FH. For that purpose, we investigated lipoprotein lipids, cholesterol precursors (squalene, methyl, and demethyl sterols), cholestanol, and plant sterols in FH-NK newborns (n = 5), non-FH siblings (n = 7), and controls (n = 20) at birth and after 1-year follow-up in 8 FH-NK and 5 non-FH children. The sum of concentrations (micrograms per deciliter) of methyl sterol (8-monomethylsterol, methostenol, 8-dimethylsterol, 8,24-dimethylsterol, and lanosterol) and squalene was higher in FH newborns than in non-FH siblings but overlapped with one control case. Cord-blood total or LDL cholesterol values could not be used for diagnostic purposes, whereas 1-year LDL cholesterol values were highly superior to those measured at birth. The methyl sterol ratio in cord blood was 29 to 193 10(2) mmol/mol cholesterol and was undetectable in serum at the age of 1 year; those of the demethyl precursor sterols were 1.5 to 8 times higher in cord blood than in serum at the age of 1 year, suggesting that cholesterol synthesis was markedly increased at birth. Plant sterols, not synthesized in human beings, were already present in serum of all the groups at birth, indicating their transfer, apparently with cholesterol, from mother to fetus. Babies born to FH mothers showed a greater tendency toward accelerated cholesterol synthesis than did those born to FH fathers. Despite signs of markedly high but similar synthesis of cholesterol at birth in FH and non-FH newborns, the diagnosis of FH was questionable by measurement of cholesterol precursors or LDL cholesterol in cord blood. The latter measurement, at the 1-year mark, is superior for diagnostic purposes.