Analysis of Children and Adolescents with Familial Hypercholesterolemia

作者：Minicocci Ilenia; Pozzessere Simone; Prisco Cristina; Montali Anna; di Costanzo Alessia; Martino Eliana; Martino Francesco; Arca Marcello

来源：Journal of Pediatrics, 2017, 183: 100-+.

DOI：10.1016/j.jpeds.2016.12.075

Objective To evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia (FH)-causative mutations in unselected children with hypercholesterolemia.
Study design LDLR, APOB, and PCSK9 genes were sequenced in 78 children and adolescents (mean age 8.4 +/- 3.7 years) with clinically diagnosed FH. The presence of polygenic hypercholesterolemia was further evaluated by genotyping 6 low-density lipoprotein cholesterol (LDL-C)-raising single-nucleotide polymorphisms.
Results Thirty-nine children (50.0%) were found to carry LDLR mutant alleles but none with APOB or PCSK9 mutant alleles. Overall, 27 different LDLR mutations were identified, and 2 were novel. Children carrying mutations showed higher LDL-C (215.2 +/- 52.7 mg/dL vs 181.0 +/- 44.6 mg/dL, P <.001) and apolipoprotein B levels (131.6 +/- 38.3 mg/dL vs 100.3 +/- 30.0 mg/dL, P <.004), compared with noncarriers. A LDL-C of similar to 190 mg/dL was the optimal value to discriminate children with and without LDLR mutations. When different diagnostic criteria were compared, those proposed by the European Atherosclerosis Society showed a reasonable balance between sensitivity and specificity in the identification of LDLR mutations. In children without mutation, the FH phenotype was not caused by the aggregation of LDL-C raising single-nucleotide polymorphisms.
Conclusions In unselected children with hypercholesterolemia, LDL-C levels > 190 mg/dL and a positive family history of hypercholesterolemia appeared to be the most reliable criteria for detecting FH. As 50% of children with suspected FH did not carry FH-causing mutations, genetic testing should be considered.

• 出版日期2017-4