Genetics, Screening, and Treatment of Familial Hypercholesterolemia: Experience Gained From the Implementation of the Vietnam Familial Hypercholesterolemia Registry.

Hong-An Le,Doan-Loi Do,Ngoc-Thanh Kim,Thanh-Huong Truong,Thanh-Tung Le,Mai-Ngoc Thi Nguyen

doi:10.3389/fgene.2020.00914

Abstract

Familial hypercholesterolemia (FH) is underdiagnosed and undertreated in a majority of the low- and middle-income countries. FH registries could prove useful in bridging the knowledge gaps, supporting genetic and clinical research, and improving health-care planning and patient care. Here, we report the first usage experience of the Vietnam FH (VINAFH) Registry. The VINAFH Registry was established in 2016 as a long-term database for prospective cohorts. FH patients were detected based on the opportunistic and cascade screening. Diagnosis of FH was assessed using the Dutch Lipid Clinic Network criteria, plasma levels of low-density lipoprotein (LDL) cholesterol, and genetic testing. To date, a total of 130 patients with FH have been registered, with 48 index cases and 82 relatives. Of the 130 patients, 8 were homozygous FH patients and 38 were children. Of FH individuals, 46.7% was confirmed by genetic testing: 61 patients (96.8%) carried the LDLR mutation (c.681C > G, c.1427C > G, c.1187-?_2140 ± ?del, c.2529_2530delinsA), and two patients (3.2%) carried the PCSK9 (protein convertase subtilisin/kexin type 9) mutation (c.42_43insTG). The c.2529_2530delinsA mutation detected in this study is novel and reported only in the Vietnamese population. However, only 53.8% of FH patients were followed up post diagnosis, and only 15.3% of these were approved for lipid-lowering therapy and specialized care. Notably, factors such as knowledge about FH in patients and/or guardians of FH children and support of primary care physicians affected patient participation with respect to treatment strategies and follow-up. Genetic identification, screening, and treatment of FH were feasible in Vietnam. The VINAFH Registry significantly contributed to the formation of the government agencies legislative acts that established the importance of FH as a socially and medically important disease requiring appropriate management strategies. Other low- and middle-income countries could, thus, use the VINAFH Registry model as a reference to establish programs for FH management according to the current status.

Highlights

Familial hypercholesterolemia (FH) is a common inherited disorder, affecting one in 250 individuals. This disease is characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) that facilitates the development of atherosclerosis, premature coronary artery disease (CAD), and mortality (Neil et al, 2004; Cuchel et al, 2014)
We previously reported the identification of LDL receptor (LDLR) p.Pro476Arg missense variant, which occurs within the gene encoding the EGF spacer domain of the LDLR, in two Vietnamese families with two homozygous for FH (HoFH) index cases and 11 heterozygous for FH (HeFH) relatives (Truong et al, 2018)
In the Vietnam FH (VINAFH) Registry cohort, we identified the novel mutation, LDLR p.Asp843Glufs∗86 frameshift variant, which occurs within the gene encoding the cytoplasmic domain of the LDLR; it was detected in a family with nine HeFH individuals

Summary

Introduction

Familial hypercholesterolemia (FH) is a common inherited disorder, affecting one in 250 individuals (de Ferranti et al, 2016; Akioyamen et al, 2017) This disease is characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) that facilitates the development of atherosclerosis, premature coronary artery disease (CAD), and mortality (Neil et al, 2004; Cuchel et al, 2014). Identification and lipid-lowering therapy play important roles in reducing the health burden for FH. Screening programs such as cascade screening, universal screening, and opportunistic screening are effective for early detection of FH (Kirke et al, 2012). Treatment for FH is still limited; for example, the CASCADE-FH Registry reported that only 48% of FH patients achieved LDL-C < 100 mg/dl and 22% achieved LDL-C < 70 mg/dl (Duell et al, 2019)

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