BACKGROUND In Malaysia, the prevalence of genetically confirmed heterozygous
familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care. CASE REPORT In this case series, we report 3 FH cases detected in primary care due to mutations in the
low-density lipoprotein receptor (LDLR),
apolipoprotein-B (
APOB), and
proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in
APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest
LDL-c level, 8.6 mmol/L, and prominent tendon
xanthomas. In case 2, the patient had an
LDL-c level of 5.7 mmol/L and premature
corneal arcus. In case 3, the patient had an
LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with
statins and therapeutic lifestyle modifications. They were referred to the
lipid specialists for up-titration of
lipid lowering medications. First-degree relatives were identified and referred for cascade testing. CONCLUSIONS This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with
lipid specialists.