A case report of heterozygous familial hypercholesterolaemia with LDLR gene mutation complicated by premature coronary artery disease detected in primary care

Abstract

Background Familial Hypercholesterolemia (FH) is an autosomal dominant genetic condition predominantly caused by the low-density lipoprotein receptor (LDLR) gene mutation. Case Summary This is the case of a 54-year-old Malay woman with genetically confirmed FH complicated by premature coronary artery disease (PCAD). She was clinically diagnosed in primary care at 52 years old, fulfilling the Simon Broome Criteria (possible FH), Dutch Lipid Clinic Criteria (score of 8: probable FH) and Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT relative risk score of 9.51). Subsequently, she was confirmed to have a heterozygous LDLR c.190+4A>T intron 2 pathogenic variant at the age of 53 years. She was known to have hypercholesterolemia and was treated with statin since the age of 25. However, the lipid-lowering agent was not intensified to achieve the recommended treatment target. The delayed FH diagnosis has caused this patient to have PCAD and percutaneous coronary intervention (PCI) at the age of 29 years and a second PCI at the age of 49 years. She also has a very strong family history of hypercholesterolemia and PCAD, where seven out of eight of her siblings were affected. Despite this, FH was not diagnosed early and cascade screening of family members was not conducted, resulting in a missed opportunity to prevent PCAD. Discussion FH can be clinically diagnosed in primary care to identify those who may require genetic testing. Multidisciplinary care focuses on improving identification, cascade screening and management of FH is vital to improving prognosis and ultimately preventing PCAD.