title: Neonatal diagnosis of familial hypercholesterolemia in newborns born to a parent with a molecularly defined heterozygous familial hypercholesterolemia.
abstract: This study was designed to compare blood lipid levels in newborn individuals with molecularly defined heterozygous familial hypercholesterolemia [FH] to those in non-affected babies and to clarify the value of lipid determinations in assessment of diagnosis of FH at birth and 1 year of age. Twenty-five babies were born to 21 parents with DNA-documented heterozygous FH. Analysis of their cord blood samples revealed 11 newborns with the FH-North Karelia [FH-NK] mutation, 3 newborns with the FH-Helsinki [FH-HKI] mutation, and 11 nonaffected newborns. Cord serum total [TC] and LDL cholesterol [LDL-C] levels (mean +/- SD) in affected newborns (2.60 +/- 0.70 and 1.77 +/- 0.56, respectively) were significantly (P < .001) higher than those in nonaffected ones (1.54 +/- 0.23 and 0.78 +/- 0.15, respectively) and another cohort of 30 randomly selected control samples from apparently healthy newborns (1.84 +/- 0.46 and 1.03 +/- 0.30, respectively). However, there was overlapping of individual lipid levels in these three groups precluding the use of TC or LDL-C determinations in neonatal diagnosis of FH. In contrast, 1 year follow-up samples from 10 affected and 7 nonaffected individuals, as well as additional samples collected from another group of 8 affected and 9 nonaffected individuals, indicated that serum cholesterol levels showed much greater increment in children with FH. Thus, at the age of 1 year the mean serum TC and LDL-C levels in the affected infants (8.38 +/- 1.18 and 7.02 +/- 1.07, respectively) were much higher (P < .001) than the corresponding levels (4.40 +/- 0.66 and 2.89 +/- 0.68, respectively) in the nonaffected infants, and the individual ranges of TC and LDL-C levels were nonoverlapping in these two groups. Serum HDL cholesterol [HDL-C] levels in 1-year-old children with FH (0.95 +/- 0.14) were approximately 20% lower than those of their similar at birth. In conclusion, phenotypic expression of heterozygous FH, as defined by molecular analysis of genomic DNA, is evident in serum LDL-C (but not HDL-C) levels already at birth, but for diagnostic purposes blood lipid determinations carried out at the age of 1 year are highly superior to those performed at birth.
authors.affiliation: Department of Medicine, University of Helsinki, Finland.
authors.forename: A F
authors.initials: AF
authors.lastname: Vuorio
authors.forename: H
authors.initials: H
authors.lastname: Turtola
authors.forename: K
authors.initials: K
authors.lastname: Kontula
mesh_terms: D000328:Adult; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D016368:Frameshift Mutation; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D007231:Infant, Newborn; D008055:Lipids / Q000097:blood*; D008297:Male; D015997:Neonatal Screening; D011973:Receptors, LDL / Q000235:genetics*; D017384:Sequence Deletion; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D011973:Receptors, LDL; D014280:Triglycerides; D002784:Cholesterol