Vuorio A F, Turtola H, Kontula K
Department of Medicine, University of Helsinki, Finland.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3332-7. doi: 10.1161/01.atv.17.11.3332.
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.
本研究旨在比较分子定义的杂合子家族性高胆固醇血症（FH）新生儿与未受影响婴儿的血脂水平，并阐明血脂测定在评估出生时和1岁时FH诊断中的价值。25名婴儿由21名有DNA记录的杂合子FH父母所生。对他们的脐带血样本分析显示，11名新生儿有FH-北卡累利阿（FH-NK）突变，3名新生儿有FH-赫尔辛基（FH-HKI）突变，11名未受影响的新生儿。受影响新生儿的脐带血清总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平（均值±标准差）（分别为2.60±0.70和1.77±0.56）显著高于未受影响新生儿（分别为1.54±0.23和0.78±0.15）以及另一组从明显健康的新生儿中随机选取的30个对照样本（分别为1.84±0.46和1.03±0.30）（P<0.001）。然而，这三组个体的血脂水平存在重叠，排除了在新生儿期使用TC或LDL-C测定来诊断FH的可能性。相比之下，10名受影响和7名未受影响个体的1年随访样本，以及从另一组8名受影响和9名未受影响个体中收集的额外样本表明，FH儿童的血清胆固醇水平升高幅度更大。因此，在1岁时，受影响婴儿的平均血清TC和LDL-C水平（分别为8.38±1.18和7.02±1.07）显著高于未受影响婴儿的相应水平（分别为4.40±0.66和2.89±0.68）（P<0.001），且这两组TC和LDL-C水平的个体范围无重叠。1岁FH儿童的血清高密度脂蛋白胆固醇（HDL-C）水平（0.95±0.14）比其出生时的类似水平低约20%。总之，通过基因组DNA分子分析定义的杂合子FH的表型表达在出生时血清LDL-C（而非HDL-C）水平中就已明显，但出于诊断目的，1岁时进行的血脂测定比出生时进行的测定具有更高的优越性。
