{"id":"4cf3de2e853d","type":"article","url":"https://hartvaat.nl/2026/01/30/familiaire-hypercholesterolemie-gemaskeerd-door-een-pcsk9-verlies-van-functievar/","title":"Familiaire hypercholesterolemie gemaskeerd door een PCSK9-verlies-van-functievariant","title_en":"Familial hypercholesterolemia concealed by a protein-truncating variant of PCSK9.","category":"cholesterol","category_label":"Cholesterol","professions":["cardioloog","internist"],"tags":["cardiovasculaire-genetica","dyslipidemie","ezetimibe","familiaire-hypercholesterolemie","familiaire-hypercholesterolemie-screening","laminopathie","ldl-cholesterol","niet-statine-therapie","pcsk9-remmers","pcsk9-remmers-nieuwe-generatie","vrouwen"],"journal":"Journal of clinical lipidology","doi":"10.1016/j.jacl.2026.01.020","source_url":"https://doi.org/10.1016/j.jacl.2026.01.020","authors":["Hayato Tada","Atsushi Furukawa","Masayuki Takamura"],"significance":5,"published":"2026-01-30","source_date":"2026-01-30","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/","https://hartvaat.nl/kennis/lipiden/genetisch-onderzoek-fh/"],"congress":"","summary_en":"A remarkable case report describes familial hypercholesterolaemia that was concealed by a co-existing PCSK9 loss-of-function variant, artificially lowering LDL-cholesterol. The case underscores the importance of genetic diagnostics when FH is suspected, even with apparently normal lipid levels.","created":"2026-07-03T10:24:55Z","updated":"2026-07-03T13:24:24Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Een opmerkelijke casus waarbij familiaire hypercholesterolemie (FH) pas laat werd ontdekt doordat een gelijktijdig aanwezige PCSK9 loss-of-function variant het LDL-cholesterol kunstmatig verlaagde. Dit onderstreept het belang van genetische diagnostiek bij verdenking op FH, zelfs bij ogenschijnlijk normale lipidewaarden.","abstract_original":"Familial hypercholesterolemia (FH) is one of the most common inherited dyslipidemias and a major risk factor for premature coronary artery disease. Statins are the primary lipid-lowering therapy for FH but are usually insufficient for reducing low-density lipoprotein cholesterol to normal levels, necessitating additional medications such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. However, the safety of long-term PCSK9 inhibition is unclear. Here, we report an extremely rare family where FH phenotypes are mitigated by co-existing familial hypobetalipoproteinemia caused by a protein-truncating variant of PCSK9. This case suggests that long-term PCSK9 inhibitor treatment may be safe and effective for patients with FH."}