Dutch Lipid Clinic Network Score – an effective tool for the diagnosis of familial hypercholesterolemia
Authors:
Katarína Rašlová 1,2; Miloslava Hučková 4; Soňa Wimmerová 3; Ján Chandoga 5; Miriama Juhosová 5
Authors‘ workplace:
Metabolické centrum, Slovenská zdravotnícka univerzita, Bratislava
1; Koordinačné centrum pre FHLP, Slovenská zdravotnícka univerzita, Bratislava
2; Fakulta verejného zdravotníctva, Slovenská zdravotnícka univerzita, Bratislava
3; Slovenská akadémia vied, Bratislava
4; Ústav lekárskej biológie, genetiky a klinickej genetiky LF UK a UNB, Bratislava
5
Published in:
AtheroRev 2025; 10(1): 62-66
Category:
Reviews
Overview
Familial hypercholesterolemia (FH) is a monogenic autosomal dominant disease, which is characterized by a high level of total and LDL-cholesterol and a high risk of atherosclerosis-related cardiovascular diseases (ASCVD). To determine the clinical diagnosis of FH, the Dutch Lipid Clinic Network Score (DLNC) is most often used, which is a prerequisite for DNA analysis of FH in Slovakia. The aim of our study was to show how the clinical diagnosis of FH based on DLNC correlates with DNA analysis of genes for LDL-receptors, APOB and PCSK9. We focused on unrelated individuals – probands. Complete data of DNA analysis, clinical and biochemical examination were available for 182 probands. Patients with primary hypercholesterolemia who had definite FH (defFH) or probable/possible FH (pFH) based on the DLNC score were compared. LDL-receptors, ApoB and PCSK9 genes were analyzed by the next generation sequencing. 102 probands were assigned to the defFH group and 89 to the pFH group. Patients with defFH were younger, had a statistically significantly higher incidence of xanthomatosis, higher levels of total cholesterol and LDL-cholesterol than patients in the pFH group (p < 0.001, resp.). We did not find a difference in the incidence of ASCVD in personal or family history. 72.5 % of patients with a clinical diagnosis of defFH had a confirmed mutation in the genes for LDL-receptors or APOB, while in the pFH group it was 25.8 % (p < 0.001). This statistically significant difference was associated with a significantly higher prevalence of mutations in the LDL-receptor gene (60.8 % vs 14.6 %; p < 0.001). The prevalence of mutations in the APOB gene did not differ between the two groups (11.8 % vs 10.1 %, ns). Not a single patient was found to have a pathological variant in the PCSK9 gene. We have shown that in the MED-PED project, DLNC is an effective criterion for the diagnosis of FH. It can be assumed that, in combination with universal FH screening in children, the detection of monogenic FH could be significantly improved and thus the effective primary prevention of early cardiovascular events.
Keywords:
Achilles tendon xanthomatosis – definite FH – Dutch Lipid Clinic Network Score –familial hypercholesterolemia (FH) – possible/probable FH
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