背景技术在马来西亚,据报道,经遗传证实的杂合子家族性高胆固醇血症(FH)的患病率为427例中的1例.尽管如此,在初级保健中,FH在很大程度上仍未得到诊断和治疗。案例报告在这个案例系列中,我们报告了3例由于低密度脂蛋白受体(LDLR)突变而在初级保健中检测到的FH病例,载脂蛋白B(APOB),和前蛋白转化酶枯草杆菌蛋白酶/kexin9型(PCSK9)基因。病例1(LDLR基因移码c.660del致病变异体)和病例2(APOB基因错义c.10579C>T致病变异体)的突变被证实为致病性,而病例3中的突变(PCSK9基因中的错义c.277C>T突变)可能是良性的。在病例1中,患者的LDL-c水平最高,8.6mmol/L,和突出的肌腱黄色瘤。在病例2中,患者的LDL-c水平为5.7mmol/L,角膜前弧。在病例3中,患者的LDL-c水平为5.4mmol/L,但没有经典的身体检查结果。遗传咨询和诊断由初级保健医生提供。这些指标病例最初在初级保健中通过他汀类药物和治疗生活方式的改变进行管理。他们被转介给脂质专家,以增加降脂药物的滴定。确定了一级亲属并进行级联测试。结论本病例系列突出显示了具有3种不同FH基因突变的患者的不同表型表达。初级保健医生应在FH指数病例的检测中发挥关键作用,基因检测,管理,对家庭成员进行级联筛查,与脂质专家合作。
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.