Compound heterozygous familial hypercholesterolemia in a Chinese boy with a de novo and transmitted low-density lipoprotein receptor mutation

Ma, Yi-Ping; Gong, Yingyun; Garg, Abhimanyu; Zhou, Hongwen

doi:10.1016/j.jacl.2017.10.005

Cited by 8 publications

(6 citation statements)

References 46 publications

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“…In previous decades, HeFH has largely been unrecognized in China because patients with HeFH exhibit a lower level of both TC and LDL-C than HeFH patients in other countries (Pimstone et al, 1998); in addition, these subjects did not manifest the usual clinical features (Sun et al, 1994). Several studies have shown the mean TC level (8.9 ± 1.8 mmol/L) and LDL-C value (6.9 ± 1.7 mmol/L) of HeFH patients (Chiou and Charng, 2016) and the mean TC level (18.2 ± 3.9 mmol/L) and LDL-C value (15.9 ± 3.7 mmol/L) of HoFH patients from China (Ma et al, 2018). Another study showed that the plasma TC and LDL-C levels were 9.1 ± 1.5 mmol/L and 7.2 ± 1.5 mmol/L, respectively, in 252 HeFH Chinese patients (mean age 37 ± 17 years, 100 males) (Hu et al, 2013), which are lower compared with the United States definite FH subjects (TC value 10.9 ± 0.49 mmol/L and LDL-C value 9.96 ± 0.04 mmol/L) (Banach et al, 2018).…”

Section: Familial Hypercholesterolemia (Fh)mentioning

confidence: 99%

“…Cao et al reported that FH is truly a common cause of coronary artery disease (CAD) in very young patients (≤ 35 years), with 38.1% of causative mutations detected in China, and the best LDL-C threshold for predicting mutations was 4.56 mmol/L (Cao et al, 2018). It is estimated that there are 2,205–4,609 HoFH patients in China (Figure 3), but only 111 cases with detailed clinical information have been reported so far (Ma et al, 2018). Most of the FH patients in mainland China are undiagnosed and untreated because there remain significant gaps in the awareness of FH among physicians and the general public in China compared with those in other Asian countries (Pang et al, 2015), and the limited data on the prevalence of FH can be due to insufficient genetic screening and national registration.…”

Section: Epidemiological Genetics Of Fhmentioning

confidence: 99%

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Current Status of Familial Hypercholesterolemia in China: A Need for Patient FH Registry Systems

Chen

Zhang

2019

Front. Physiol.

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Background: Familial hypercholesterolemia (FH) greatly facilitates the development of cardiovascular disease (CVD). Without timely treatment, the incidence of coronary heart disease (CHD) in patients with FH is 3 to 4 times that in non-FH patients, and the onset of CVD would be advanced by approximately 10 years. There is ample evidence that the diagnosis and adequate treatment of FH are not properly considered for all ethnicities. The monogenic cause of FH includes apolipoprotein B (APOB), low-density lipoprotein receptor (LDLR), and proprotein convertase subtilisin/kexin 9 (PCSK9). There are approximately 2,765,420 to 6,913,550 cases of potential heterozygous FH (HeFH) and 2,205 to 4,609 cases of potential homozygous FH (HoFH) in China. Nevertheless, China lacks clinical diagnostic criteria specific to Chinese patients, such that most FH patients cannot be diagnosed until middle age or after their first cardiovascular event, thus precluding early treatment.Objective: This article explores the gene mutations, diagnosis and treatment of FH patients in China. Following the implementation of the two-child policy, there is a need to establish Chinese FH registry systems and genetic databases and to address the challenges in conducting cascade screening and long-term management.Conclusion: Advocating the establishment of FH registry systems and databases is an important rate-limiting step in improving long-term prognosis in FH patients, so that joint efforts of clinical experts and public communities are required. We recommend a process flow from case identification to entry into the registry system, and the widespread use of the system in clinical applications can provide the best treatment guidance for medical practice.

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Section: Familial Hypercholesterolemia (Fh)mentioning

confidence: 99%

Section: Epidemiological Genetics Of Fhmentioning

confidence: 99%

Current Status of Familial Hypercholesterolemia in China: A Need for Patient FH Registry Systems

Chen

Zhang

2019

Front. Physiol.

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“…However, diagnosis and therapeutic rates among these patients remain alarmingly low (less than 5% for HoFH and less than 1% for HeFH). This highlights an urgent need to enhance awareness regarding FH among Chinese healthcare professionals as well as the general public 20 …”

Section: Discussionmentioning

confidence: 99%

Failure of lipid control by PCSK9 inhibitors in compound heterozygous familial hypercholesterolemia complicated with premature myocardial infarction: A case report

Zhang,

Yang,

Zhu

et al. 2024

Clinical Case Reports

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Key Clinical MessageA certain level of low‐density lipoprotein receptor activity is crucial for the efficacy of PCSK9i. Therapeutic strategies for familial hypercholesterolemia patients should consider drug efficacy, and genetic testing will be helpful.AbstractFamilial hypercholesterolemia (FH) is a serious autosomal dominant disorder. Managing blood lipids in FH patients poses greater challenges for clinicians. Drug therapy may not always yield satisfactory results, particularly in individuals with low‐density lipoprotein receptor (LDLR) negative mutations. Herein, we report a young female harboring an LDLR frameshift mutation. This patient developed xanthomas at 7 months old and underwent several years of treatment involving four classes of lipid‐lowering drugs, including PCSK9i. However, the response to drug therapy was limited in this patient and eventually culminated in premature myocardial infarction. The efficacy of PCSK9i depends on the activity of LDLR. The inefficacy of PCSK9i may arise from the extensive mutations which leading to loss of LDLR activity. Therapy plans for these patients should take into account the efficacy of drug therapy. Early genetic testing is crucial for clinicians to make informed decisions regarding therapy options.

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“…FH has been recognized as an autosomal codominant inherited disease, except in extremely rare situations of individuals with pathogenic variants of LDLRAP1, wherein an autosomal recessive inheritance pattern is observed [ 20 ]. Nevertheless, we can identify relatives who are affected when we diagnose a patient with FH through cascade screening because the disease has a 100% penetration rate, and only a few cases with de novo pathogenic variants have been described [ 21 ]. Genetic testing is usually not conducted for the relatives of the proband of FH because the extremely high level of LDL cholesterol is sufficient to make a diagnosis.…”

Section: Pattern Of Inheritance and Pathogenic Variants Of Fhmentioning

confidence: 99%

Genetic Counseling and Genetic Testing for Familial Hypercholesterolemia

Tada,

Kawashiri,

Nohara

et al. 2024

Genes

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Familial hypercholesterolemia (FH) is one of the most common autosomal codominant Mendelian diseases. The major complications of FH include tendon and cutaneous xanthomas and coronary artery disease (CAD) associated with a substantial elevation of serum low-density lipoprotein levels (LDL). Genetic counseling and genetic testing for FH is useful for its diagnosis, risk stratification, and motivation for further LDL-lowering treatments. In this study, we summarize the epidemiology of FH based on numerous genetic studies, including its pathogenic variants, genotype–phenotype correlation, prognostic factors, screening, and usefulness of genetic counseling and genetic testing. Due to the variety of treatments available for this common Mendelian disease, genetic counseling and genetic testing for FH should be implemented in daily clinical practice.

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Compound heterozygous familial hypercholesterolemia in a Chinese boy with a de novo and transmitted low-density lipoprotein receptor mutation

Cited by 8 publications

References 46 publications

Current Status of Familial Hypercholesterolemia in China: A Need for Patient FH Registry Systems

Current Status of Familial Hypercholesterolemia in China: A Need for Patient FH Registry Systems

Failure of lipid control by PCSK9 inhibitors in compound heterozygous familial hypercholesterolemia complicated with premature myocardial infarction: A case report

Genetic Counseling and Genetic Testing for Familial Hypercholesterolemia

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