The Prevalence of Heterozygous Familial Hypercholesterolemia among Adult Filipino Patients with Dyslipidemia at Universidad de Santa Isabel Health Services Department: An Observational Descriptive Prospective Study

Objectives: It is to determine the prevalence of familial hypercholesterolemia (FH) among adult Filipino patients with dyslipidemia at Universidad de Santa Isabel Health Services Department in one year. Methods: An observational descriptive prospective study involves Filipino patients, aged 19 years and older, with dyslipidemia. The Dutch Lipid Network (DLN) Criteria was used to diagnose FH. Prevalence data and categorical variables were expressed as percentages, while continuous variables were reported as mean and standard deviations. Results: 529 patients were included in the study. 302 were females, and 227 were males. 180 (34%) scored Unlikely, 100 (19%) scored Probable, 185 (35%) scored Possible, and 64 (12%) were classified under Definite Familial Hypercholesterolemia. Most of the patients diagnosed with definite FH did not have diabetes, cerebrovascular disease (CVD), and coronary artery disease (CAD). The diagnosis was not affected by gender, BMI, smoking, and alcohol consumption. Hypertension was significantly correlated to the diagnosis of FH, as most of them were already hypertensive at diagnosis. It was noted that hypertension, diabetes, CVD, and CAD were seen at an earlier age among patients with definite FH. Conclusion: The prevalence of heterozygous FH at 12% among dyslipidemia patients and 1.3% among the general population was described for the first time in our region. This result should raise the awareness of our healthcare providers that FH, which is a major risk factor for premature CAD and CVD, exists, and early detection and management are important.

Ezetimibe Completely Replaced LDL-Apheresis for the Treatment of Familial Hypercholesterolemia and Coronary Artery Disease after CABG—A Case Report

Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotein bound cholesterol-apheresis can be used to treat very severe cases of familial hypercholesterolemia. However, statins are not always effective on their own and, recently, ezetimibe has emerged as a unique anti- hypercholesterolemic drug that acts as a cholesterol transporter inhibitor;its role is only partially understood. I experienced rare case that appeared to benefit from ezetimibe therapy, and report them as they help increase our knowledge of this novel drug.

Characterization of coronary atherosclerotic plaques in a homozygous familial hypercholesterolemia visualized by optical coherence tomography

Familial hypercholesterolemia(FH)is an autosomal dominant genetic disorder,which resulted in severe elevations in low-density lipoprotein cholesterol(LDL-C)and a markedly increased risk of early-onset coronary disease.[1]t is most frequently caused by loss-of-function mutations in genes affecting the LDL receptor,which clears LDL particles from plasma.

Clinical,biochemical and genetic characteristics of familial hypercholesterolemia with and without type 2 diabetes

Background Though type 2 diabetes mellitus(T2DM)is an important and independent risk factor for coronary artery disease(CAD)in general population,whether this feature also exists in patients with familial hypercholesterolemia(FH)is less determined.The current study aims to characterize the clinical,laboratory,coronary and genetic characteristics of the FH patients with T2DM compared with FH alone.

Accelerated Atherosclerosis in a Young Female with Familial Hypercholesterolemia

Familial hypercholesterolemia is an autosomal dominant genetic disease due to mutation in low-density lipoprotein-cholesterol receptor gene. It is characterized by elevated plasma low-density lipoprotein-cholesterol and the consequence of which leads to premature cardiovascular disease. The mainstay in the management of familial hypercholesterolemia patient is the treatment with high potency statin. However, current research shows influence of the type of low-density lipoprotein-cholesterol receptor mutations on severity of the cardiovascular disease, lipid profile, and response to statin treatment. We are here presenting a case of young Indian female patient who was diagnosed with familial hypercholesterolemia and treated with percutaneous transluminal coronary angioplasty in view of double vessel disease in the third decade of her life. She was prescribed with statin therapy for elevated low-density lipoprotein cholesterol. After 3 years, she presented once again with a triple vessel disease along with patent stented segments and abnormal lipid profile.

Familial Hypercholesterolemia with Two Mutations in LDLR Gene: A Case Report and Literature Review

We report a case of Familial hypercholesterolemia (FH) with two mutations in low density lipoprotein receptor (LDLR) gene and speculate the correlation between the newly discovered mutation type of LDLR gene and FH. We collected and analyzed the clinical data of the proband in the case and her immediate family members, and detected the LDLR, Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK-9) and Apolipoprotein B (Apo B) gene in the peripheral blood of all the participants. We found that the curative effect of the patient is limited, but no obvious complication was detected. Genetic testing results pointed out that there were two mutations in the patient’s LDLR gene. One was p.W483* mutation in exon 10 (c. 1448 G > A), another was p.T534I mutation in exon 11 (c. 1601 C > T). The p. W483* mutation in exon 10 was detected in the father and sister, additionally p. T534I mutation in exon 11 was detected in the mother. Both the two LDLR gene mutations are inherited from her parents. We hypothesize that the patient in this case was a complex heterozygote. The newly discovered mutation gene (T534I) may be one of the important causes of dyslipidemia in patients, and its adverse effects are more serious than W483* which have been reported. Also, we predict that the T534I mutation will not cause serious early onset of cardiovascular complications.

Pleomorphic cutaneous xanthomas disclosing homozygous familial hypercholesterolemia

Homoxygous Familial Hypercholesterolemia is characterized by a presence of several types of cutaneous xanthomas with an abnormal lipid profile. Some of these could be pathognomonic. Although these could be initially interpreted as isolated and localized benign disorders and offered surgical treatment, it has become increasingly clear that they could be a part of a systemic pathology. Here we describe a case of this rare disorder in a 19 years old non-obese young man who presented multiple, intertriginous, tuberous and tendinous xanthomas and had an associated abnormal lipid profile with elevated lowdensity lipoprotein cholesterol levels. A detailed history with clinical assessment in the differential diagnosis and laboratory investigations led to a precise diagnosis.

Two cases of familial hypercholesterolemia with premature acute coronary syndrome:Case report

Objective:To investigate the clinical characteristics of familial hypercholesterolemia and early-onset acute coronary syndrome(ACS),in order to improve the understanding and diagnosis and treatment of the disease.Methods:We retrospectively studied the clinical data of 2 patients with familial hypercholesterolemia and premature acute coronary syndrome treated in the Department of Cardiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology.All patients underwent genetic testing and coronary artery angiography.Results:Two patients were heterozygous familial hypercholesterolemia by gene test.Coronary artery angiography showed that three coronary arteries had serious lesions,which recovered well after drug and surgical treatment.Conclusion:Patients with familial hypercholesterolemia were prone to early onset of acute coronary syndrome,which should be identified,diagnosed and treated as soon as possible.

A Pedigree Analysis of a Family With Familial Hypercholesterolemia

Objective The current study was designed to investigate the features of a family with familial hypercholesterolemia(FH). Methods Twenty members of three generations in a family with FH were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. Results The proband was a 41 years old male who suffered from angina pectoris with multi-vessel stenosis of coronary artery at the age of 40. Among 20 members, 8 individuals were demonstrated with hypercholes-terolemia in this family with the total incidence of 40% [54.5% (6/11) in male and 22. 2% (2/9) in femaleThe serum total cholesterol level was elevated in childhood from 7. 1 to 10. 8 mmol/L and tended to be raised with increasing age. In addition, the level of total cholesterol was found to be elevated both in a monozy-gote twin brothers and their offspring in the family. Conclusion FH appears to be a hereditary disease of autosomal dominance inheritance and the outcome of FH patients with coronary heart disease seems to be poor in prognosis.

Familial Hypercholesterolemia in an Azorean Family:A Novel Mutation in the Low-Density Lipoprotein Receptor Gene

Familial hypercholesterolemia (FH) is one of the most prevalent autosomal dominant inherited disorders. Mutations have been found in at least 3 genes: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). We report on an Azorean family with FH due to a novel mutation in the LDLR gene across three generations. The index-case was first seen at our endocrinology consultation at 12 years old, because of delayed growth and development. Laboratorial investigations revealed a complete failure of the anterior hypophysis due to a congenital malformation of the sella turcica. A total cholesterol of 313 mg/dL (90 - 190 mg/dL) and low-density lipoprotein cholesterol (LDL-C) of 262 mg/dL (<115 mg/dL) was found in routine blood tests. There was a paternal history of hypercholesterolemia, corneal arcus and myocardial infarction at an early age. Screening for mutations in LDLR gene was carried out. &#73n the affected cases, an intronic heterozygous point mutation (c.818-3C > G) causing a premature termination of transcription (stop codon) was identified.

Prevalence of Cardiovascular Risk Factors and Heterozygous Familial Hypercholesterolemia in Premature Atherosclerotic Patients Presenting with Acute Coronary Syndrome

Background: Heterozygous familial hypercholesterolemia is an autosomal dominant genetic disorder with an estimated prevalence of 1/200 - 1/500 in the general population. Early identification of patient with familial hypercholesterolemia is important, because appropriate treatment may reduce the risk of premature atherosclerosis. Objective: Assessment of the prevalence of different modifiable cardiovascular risk factors and clinical diagnosis of heterozygous familial hypercholesterolemia. Methods: One hundred patients were enrolled, included young patients (males less than 50 years and females less than 60 years old) presented with first attack of acute coronary syndrome either ST elevation myocardial infarction (STEMI), non ST elevation myocardial infarction (NSTEMI) or unstable angina (UA). All patients were subjected to full history taking, general and local examination, Electrocardiogram, transthoracic Echocardiography, laboratory investigations, coronary angiography and Dutch score calculation for familial hyperlipidemias. Results: The mean level of serum cholesterol among studied group was 268.31 ± 59.33, HDL-C was 39.63 ± 7.52, LDL was 192.27 ± 60.61 and TG was 180.10 ± 39.64. With application of Dutch score, 20% of patients diagnosed definite familial hypercholesterolemia with Dutch score > 8. Twenty-six percent of patients diagnosed as probable familial hypercholesterolemia with Dutch score 6 - 8. Thirty-nine percent patients diagnosed as possible familial hypercholesterolemia with Dutch score 3 - 5 and 15% of patients were unlikely familial hypercholesterolemia with Dutch score < 3 with significant correlation between Dutch score and age, total cholesterol, LDL-C, serum creatinine. Conclusion: Familial hypercholesterolemia (FH) is one of the most common serious genetic disorders of cholesterol metabolism. The early identification of heterogynous FH patients is crucial to start an effective prevention strategy.

Imaging the Atherosclerosis with 64-Detector Row Computed Tomography in Homozygous Familial Hypercholesterolemia

Objective: The higher risk and fatality of cardiovascular disease in subjects with homozygous familial hypercholesterolemia warrants early screening. Computed tomography angiography is the most promising method at present as a reliable and reproducible noninvasive diagnostic test of cardiovascular disease. We aimed to describe the 64-slice multidetector computed tomography coronary angiography findings of new cases with homozygous familial hypercholesterolemia. Methods: Four patients with homozygous familial hypercholesterolemia (2 female and 2 male) with mean age of 23 ± 9 years were included. Mean plasma total and LDL cholesterol were 654 ± 75 mg/dl and 609 ± 76 mg/dl. Tomography examinations were performed using a 64-row MDCT-CA system (Brilliance Computed Tomography scanner, Philips Healthcare). Results: All patients presented calcified and mixed atherosclerotic plaques in the ascending aorta near the origin of the coronary arteries. More extensive atherosclerosis was found in Case 1 and Case 2 than in other cases. Case 3 has mild atherosclerosis and Case 4 had normal coronaries but plaques in aorta. In addition, we detected myocardial bridging in left anterior descending artery of 2 cases, calcified plaques in postero-lateral branch artery, and calcification in non-coronary sinus in others. Conclusion: Multidetector computed tomography coronary angiography is a useful, non-invasive tool for detecting early aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia subjects and may be the choice of imaging for most of such subjects.

Genetically confirmed familial hypercholesterolemia in outpatients with hypercholesterolemia

BackgroundFamilial 血胆脂醇过多(FH ) 是能导致早熟的冠的心疾病(pCHD ) 的脂蛋白新陈代谢的正染色体的主导的混乱。在中国有大约 380 万个潜在的 FH 病人，而 FH 的临床、基因的数据是 limited.MethodsDutch 类脂化合物诊所网络(DLCN ) 标准被用来与血胆脂醇过多在门诊病人诊断 FH。与定序确认的 Sanger 相结合的重新定序的薄片分析被用来根据 DLCN 标准在明确的 FH 病人识别变化。在 silico，分析与以前未知的致病力在变化被进行。然后，新奇变异的受体是进人的胚胎肾 293 的 transfected (HEK-293 ) 房间。绑定和变异的受体的成为主观活动被明确的 FH 的流动 cytometry.ResultsThe 流行在这研究与血胆脂醇过多在门诊病人分析是 3.2% 。用基因测试，一同型结合的 FH (HoFH ) ，一异质接合的 FH (HeFH ) 和三复合异质接合的 FH，病人们被证实。在低密度的脂蛋白的八个变化受体(LDLR ) 基因被识别，在哪个 c.357delG 是一个新奇变化并且与 FH 显型共同分离。生物信息的分析证实 c.357delG 是一个病原的变化。而且，当与由流动 cytometry 分析，绑定和成为主观的野类型的 LDLR 相比 c.357delG 异种 LDLR 的活动被 35% 和 49% 减少时， respectively.ConclusionsThis 学习与明确的 FH， c.357delG 在是一个新奇病原的变化在五个病人识别了八个 LDLR 基因变化。这些调查结果增加我们在中国的 FH 的基因光谱的理解。

PML nuclear bodies:new players in familial amyotrophic lateral sclerosis-frontotemporal dementia?

Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al.,2013).The major pathological hallmark of ALS and FTD are the depletion from the nucleus of the RNA-binding proteins TAR DNA‐binding protein 43(TDP-43)and FUsed in Sarcoma(FUS)and their abnormal accumulation in ubiquitin-positive cytoplasmic inclusions(Ling et al.,2013).

LDL-C rebound after long-term evolocumab treatment and intravascular imaging evidence in a familial hypercholesterolemia patient with early-onset myocardial infarction

Patients with familial hypercholesterolemia(FH)have elevated low-density lipoprotein cholesterol(LDL-C)levels and are at high risk of premature cardiovascular disease.1 Heterozygous FH(HeFH)is one of the commonest genetic disorders,and is more frequent among those with ischemic heart disease(IHD),atherosclerotic cardiovascular disease(ASCVD)and premature IHD.

Development of immature ovarian teratoma after mature teratoma in a girl with familial ovarian teratoma:A case report

BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of the ovary in an adolescent female with a family history of ovarian teratoma.CASE SUMMARY A 16-year-old girl who had undergone bilateral ovarian cystectomy for mature teratomas 3 years ago showed bilateral adnexal tumors during her regular ultrasonography follow-up every 6 months.She received laparoscopic bilateral ovarian cystectomy,and final histopathology showed grade-1 immature teratoma of the left ovary and mature teratoma of the right ovary.Laparoscopic left salpingo-oophorectomy and staging procedures were performed again.Her mother,maternal aunt,and maternal grandmother had also received surgeries for mature ovarian teratomas.CONCLUSION It is important to have guidance on management of patient and family members with familial ovarian teratomas.

Novel subtype of obesity influencing the outcomes of sleeve gastrectomy:Familial aggregation of obesity

BACKGROUND Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy(SG)between patients with familial aggregation of obesity(FAO)and patients with sporadic obesity(SO)have not been elucidated.AIM To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO.METHODS A total of 193 patients with obesity who underwent SG were selected.Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity(1 SO vs 1FAO,2SO vs 2FAO).The baseline characteristics,weight loss outcomes,prevalence of obesity-related comorbidities and incidence of major surgeryrelated complications were compared between groups.RESULTS We defined FAO as the presence of two or more first-degree relatives with obesity.Patients with FAO did not initially show significant differences in baseline data,short-term postoperative weight loss,or obesity-related comorbidities when compared to patients with SO preoperatively.However,distinctions between the two groups became evident at the two-year mark,with statistically significant differences in both percentage of total weight loss(P=0.006)and percentage of excess weight loss(P<0.001).The FAO group exhibited weaker remission of type 2 diabetes mellitus(T2DM)(P=0.031),hyperlipidemia(P=0.012),and non-alcoholic fatty liver disease(NAFLD)(P=0.003)as well as a lower incidence of acid reflux(P=0.038).CONCLUSION FAO patients is associated with decreased mid-to-long-term weight loss outcomes;the alleviation of T2DM,hyperlipidemia and NAFLD;and decreased incidence of acid reflux postoperatively.

Prevalence of familial hypercholesterolemia and its association with coronary artery disease:A Chinese cohort study

Background:Familial hypercholesterolemia(FH)is underrecognized,and its association with coronary artery disease(CAD)remains limited,especially in China.We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort.Methods:FH was defined using the Make Early Diagnosis to Prevent Early Death(MEDPED)criteria.The crude and age-sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR)project during 2007−2008.The associations of FH with incident CAD and its major subtypes were estimated with the cohort-stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow-up(2018−2020).Results:Among 98,885 included participants,190 participants were defined as FH.Crude and age−sex standardized prevalence and 95%confidence interval(CI)of FH were 0.19%(0.17%-0.22%)and 0.13%(0.10%-0.16%),respectively.The prevalence varied across age groups and peaked in the group of 60-<70 years(0.28%),and the peak prevalence(0.18%)in males was earlier,yet lower than the peak crude prevalence in females(0.41%).During a mean follow-up of 10.7 years,2493 cases of incident CAD were identified.After multivariate adjustment,FH patients had a 2.03-fold greater risk of developing CAD compared to non-FH participants.Conclusions:The prevalence of FH was estimated to be 0.19%in the participants,and it was associated with an elevated risk of incident CAD.Our study suggests that early screening of FH has certain public health significance for the prevention of CAD.

Prognostic implication of early posttransplant hypercholesterolemia in liver transplantation for patients with hepatocellular carcinoma

Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC(recurrence HR = 0.306, P = 0.011;mortality HR = 0.325, P = 0.031).Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.

Familial Lateral Sclerosis with Juvenile Onset: About 3 Cases and Review of the Literature

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease deadly. In Africa, little data exists on this condition and the form familial is the most common with a younger age of onset. Our observations relate to three brothers, born from a consanguineous marriage. The diagnosis of amyotrophic lateral sclerosis was certain placed in all patients according to the criteria of Awaji. The average age of patients was 16.66 years, and the average age of onset of symptoms was 10.33 years old. The female gender was the most represented with a sex ratio of 0.5. Our patients benefited from rilusole, vitamin D and physiotherapy. A only patient presented with dysphagia. However, no cases have been observed at this day.